Research activity information

• Pcgf1 gene disruption reveals primary involvement of epigenetic mechanism in neuronal subtype specification in the enteric nervous system.

  Bayu Pratama Putra, Keisuke Ito, Carla Cirillo, Mukhamad Sunardi, Haruhiko Koseki, Toshihiro Uesaka, Hideki Enomoto

  The enteric nervous system (ENS) regulates gut functions independently from the central nervous system (CNS) by its highly autonomic neural circuit that integrates diverse neuronal subtypes. Although several transcription factors are shown to be necessary for the generation of some enteric neuron subtypes, the mechanisms underlying neuronal subtype specification in the ENS remain elusive. In this study, we examined the biological function of Polycomb group RING finger protein 1 (PCGF1), one of the epigenetic modifiers, in the development and differentiation of the ENS by disrupting the Pcgf1 gene selectively in the autonomic-lineage cells. Although ENS precursor migration and enteric neurogenesis were largely unaffected, neuronal differentiation was impaired in the Pcgf1-deficient mice, with the numbers of neurons expressing somatostatin (Sst+ ) decreased in multiple gut regions. Notably, the decrease in Sst+ neurons was associated with the corresponding increase in calbindin+ neurons in the proximal colon. These findings suggest that neuronal subtype conversion may occur in the absence of PCGF1 and that epigenetic mechanism is primarily involved in specification of some enteric neuron subtypes. This article is protected by copyright. All rights reserved.

  Jul. 2023, Development, growth & differentiation, English, Domestic magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• A single RET mutation in Hirschsprung disease induces intestinal aganglionosis via a dominant-negative mechanism

  Mukhamad Sunardi, Keisuke Ito, Yuya Sato, Toshihiro Uesaka, Mitsuhiro Iwasaki, Hideki Enomoto

  Elsevier BV, Dec. 2022, Cellular and Molecular Gastroenterology and Hepatology

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Uts2b is a microbiota-regulated gene expressed in vagal afferent neurons connected to enteroendocrine cells producing cholecystokinin.

  Yuta Yoshioka, Yoshihisa Tachibana, Toshihiro Uesaka, Hiroyuki Hioki, Yuya Sato, Takumi Fukumoto, Hideki Enomoto

  Enteroendocrine cells (EECs) are the primary sensory cells that sense the gut luminal environment and secret hormones to regulate organ function. Recent studies revealed that vagal afferent neurons are connected to EECs and relay sensory information from EECs to the brain stem. To date, however, the identity of vagal afferent neurons connected to a given EEC subtype and the mode of their gene responses to its intestinal hormone have remained unknown. Hypothesizing that EEC-associated vagal afferent neurons change their gene expression in response to the microbiota-related extracellular stimuli, we conducted comparative gene expression analyses of the nodose-petrosal ganglion complex (NPG) using specific pathogen-free (SPF) and germ-free (GF) mice. We report here that the Uts2b gene, which encodes a functionally unknown neuropeptide, urotensin 2B (UTS2B), is expressed in a microbiota-dependent manner in NPG neurons. In cultured NPG neurons, expression of Uts2b was induced by AR420626, the selective agonist for FFAR3. Moreover, distinct gastrointestinal hormones exerted differential effects on Uts2b expression in NPG neurons, where cholecystokinin (CCK) significantly increased its expression. The majority of Uts2b-expressing NPG neurons expressed CCK-A, the receptor for CCK, which comprised approximately 25% of all CCK-A-expressing NPG neurons. Selective fluorescent labeling of Uts2b-expressing NPG neurons revealed a direct contact of their nerve fibers to CCK-expressing EECs. This study identifies the Uts2b as a microbiota-regulated gene, demonstrates that Uts2b-expressing vagal afferent neurons transduce sensory information from CCK-expressing EECs to the brain, and suggests potential involvement of UTS2B in a modality of CCK actions.

  Jun. 2022, Biochemical and biophysical research communications, 608, 66 - 72, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network

  Mathys Grapotte, Manu Saraswat, Chloé Bessière, Christophe Menichelli, Jordan A. Ramilowski, Jessica Severin, Yoshihide Hayashizaki, Masayoshi Itoh, Michihira Tagami, Mitsuyoshi Murata, Miki Kojima-Ishiyama, Shohei Noma, Shuhei Noguchi, Takeya Kasukawa, Akira Hasegawa, Harukazu Suzuki, Hiromi Nishiyori-Sueki, Martin C. Frith, Imad Abugessaisa, Stuart Aitken, Bronwen L. Aken, Intikhab Alam, Tanvir Alam, Rami Alasiri, Ahmad M. N. Alhendi, Hamid Alinejad-Rokny, Mariano J. Alvarez, Robin Andersson, Takahiro Arakawa, Marito Araki, Taly Arbel, John Archer, Alan L. Archibald, Erik Arner, Peter Arner, Kiyoshi Asai, Haitham Ashoor, Gaby Astrom, Magda Babina, J. Kenneth Baillie, Vladimir B. Bajic, Archana Bajpai, Sarah Baker, Richard M. Baldarelli, Adam Balic, Mukesh Bansal, Arsen O. Batagov, Serafim Batzoglou, Anthony G. Beckhouse, Antonio P. Beltrami, Carlo A. Beltrami, Nicolas Bertin, Sharmodeep Bhattacharya, Peter J. Bickel, Judith A. Blake, Mathieu Blanchette, Beatrice Bodega, Alessandro Bonetti, Hidemasa Bono, Jette Bornholdt, Michael Bttcher, Salim Bougouffa, Mette Boyd, Jeremie Breda, Frank Brombacher, James B. Brown, Carol J. Bult, A. Maxwell Burroughs, Dave W. Burt, Annika Busch, Giulia Caglio, Andrea Califano, Christopher J. Cameron, Carlo V. Cannistraci, Alessandra Carbone, Ailsa J. Carlisle, Piero Carninci, Kim W. Carter, Daniela Cesselli, Jen-Chien Chang, Julie C. Chen, Yun Chen, Marco Chierici, John Christodoulou, Yari Ciani, Emily L. Clark, Mehmet Coskun, Maria Dalby, Emiliano Dalla, Carsten O. Daub, Carrie A. Davis, Michiel J. L. de Hoon, Derek de Rie, Elena Denisenko, Bart Deplancke, Michael Detmar, Ruslan Deviatiiarov, Diego Di Bernardo, Alexander D. Diehl, Lothar C. Dieterich, Emmanuel Dimont, Sarah Djebali, Taeko Dohi, Jose Dostie, Finn Drablos, Albert S. B. Edge, Matthias Edinger, Anna Ehrlund, Karl Ekwall, Arne Elofsson, Mitsuhiro Endoh, Hideki Enomoto, Saaya Enomoto, Mohammad Faghihi, Michela Fagiolini, Mary C. Farach-Carson, Geoffrey J. Faulkner, Alexander Favorov, Ana Miguel Fernandes, Carmelo Ferrai, Alistair R. R. Forrest, Lesley M. Forrester, Mattias Forsberg, Alexandre Fort, Margherita Francescatto, Tom C. Freeman, Martin Frith, Shinji Fukuda, Manabu Funayama, Cesare Furlanello, Masaaki Furuno, Chikara Furusawa, Hui Gao, Iveta Gazova, Claudia Gebhard, Florian Geier, Teunis B. H. Geijtenbeek, Samik Ghosh, Yanal Ghosheh, Thomas R. Gingeras, Takashi Gojobori, Tatyana Goldberg, Daniel Goldowitz, Julian Gough, Dario Greco, Andreas J. Gruber, Sven Guhl, Roderic Guigo, Reto Guler, Oleg Gusev, Stefano Gustincich, Thomas J. Ha, Vanja Haberle, Paul Hale, Bjrn M. Hallstrom, Michiaki Hamada, Lusy Handoko, Mitsuko Hara, Matthias Harbers, Jennifer Harrow, Jayson Harshbarger, Takeshi Hase, Akira Hasegawa, Kosuke Hashimoto, Taku Hatano, Nobutaka Hattori, Ryuhei Hayashi, Yoshihide Hayashizaki, Meenhard Herlyn, Kristina Hettne, Peter Heutink, Winston Hide, Kelly J. Hitchens, Shannon Ho Sui, Peter A. C. ’t Hoen, Chung Chau Hon, Fumi Hori, Masafumi Horie, Katsuhisa Horimoto, Paul Horton, Rui Hou, Edward Huang, Yi Huang, Richard Hugues, David Hume, Hans Ienasescu, Kei Iida, Tomokatsu Ikawa, Toshimichi Ikemura, Kazuho Ikeo, Norihiko Inoue, Yuri Ishizu, Yosuke Ito, Masayoshi Itoh, Anna V. Ivshina, Boris R. Jankovic, Piroon Jenjaroenpun, Rory Johnson, Mette Jorgensen, Hadi Jorjani, Anagha Joshi, Giuseppe Jurman, Bogumil Kaczkowski, Chieko Kai, Kaoru Kaida, Kazuhiro Kajiyama, Rajaram Kaliyaperumal, Eli Kaminuma, Takashi Kanaya, Hiroshi Kaneda, Philip Kapranov, Artem S. Kasianov, Takeya Kasukawa, Toshiaki Katayama, Sachi Kato, Shuji Kawaguchi, Jun Kawai, Hideya Kawaji, Hiroshi Kawamoto, Yuki I. Kawamura, Satoshi Kawasaki, Tsugumi Kawashima, Judith S. Kempfle, Tony J. Kenna, Juha Kere, Levon Khachigian, Hisanori Kiryu, Mami Kishima, Hiroyuki Kitajima, Toshio Kitamura, Hiroaki Kitano, Enio Klaric, Kjetil Klepper, S. Peter Klinken, Edda Kloppmann, Alan J. Knox, Yuichi Kodama, Yasushi Kogo, Miki Kojima, Soichi Kojima, Norio Komatsu, Hiromitsu Komiyama, Tsukasa Kono, Haruhiko Koseki, Shigeo Koyasu, Anton Kratz, Alexander Kukalev, Ivan Kulakovskiy, Anshul Kundaje, Hiroshi Kunikata, Richard Kuo, Tony Kuo, Shigehiro Kuraku, Vladimir A. Kuznetsov, Tae Jun Kwon, Matt Larouche, Timo Lassmann, Andy Law, Kim-Anh Le-Cao, Charles-Henri Lecellier, Weonju Lee, Boris Lenhard, Andreas Lennartsson, Kang Li, Ruohan Li, Berit Lilje, Leonard Lipovich, Marina Lizio, Gonzalo Lopez, Shigeyuki Magi, Gloria K. Mak, Vsevolod Makeev, Riichiro Manabe, Michiko Mandai, Jessica Mar, Kazuichi Maruyama, Taeko Maruyama, Elizabeth Mason, Anthony Mathelier, Hideo Matsuda, Yulia A. Medvedeva, Terrence F. Meehan, Niklas Mejhert, Alison Meynert, Norihisa Mikami, Akiko Minoda, Hisashi Miura, Yohei Miyagi, Atsushi Miyawaki, Yosuke Mizuno, Hiromasa Morikawa, Mitsuru Morimoto, Masaki Morioka, Soji Morishita, Kazuyo Moro, Efthymios Motakis, Hozumi Motohashi, Abdul Kadir Mukarram, Christine L. Mummery, Christopher J. Mungall, Yasuhiro Murakawa, Masami Muramatsu, Mitsuyoshi Murata, Kazunori Nagasaka, Takahide Nagase, Yutaka Nakachi, Fumio Nakahara, Kenta Nakai, Kumi Nakamura, Yasukazu Nakamura, Yukio Nakamura, Toru Nakazawa, Guy P. Nason, Chirag Nepal, Quan Hoang Nguyen, Lars K. Nielsen, Kohji Nishida, Koji M. Nishiguchi, Hiromi Nishiyori, Kazuhiro Nitta, Shuhei Noguchi, Shohei Noma, Cedric Notredame, Soichi Ogishima, Naganari Ohkura, Hiroshi Ohno, Mitsuhiro Ohshima, Takashi Ohtsu, Yukinori Okada, Mariko Okada-Hatakeyama, Yasushi Okazaki, Per Oksvold, Valerio Orlando, Ghim Sion Ow, Mumin Ozturk, Mikhail Pachkov, Triantafyllos Paparountas, Suraj P. Parihar, Sung-Joon Park, Giovanni Pascarella, Robert Passier, Helena Persson, Ingrid H. Philippens, Silvano Piazza, Charles Plessy, Ana Pombo, Fredrik Ponten, Stéphane Poulain, Thomas M. Poulsen, Swati Pradhan, Carolina Prezioso, Clare Pridans, Xiang-Yang Qin, John Quackenbush, Owen Rackham, Jordan Ramilowski, Timothy Ravasi, Michael Rehli, Sarah Rennie, Tiago Rito, Patrizia Rizzu, Christelle Robert, Marco Roos, Burkhard Rost, Filip Roudnicky, Riti Roy, Morten B. Rye, Oxana Sachenkova, Pal Saetrom, Hyonmi Sai, Shinji Saiki, Mitsue Saito, Akira Saito, Shimon Sakaguchi, Mizuho Sakai, Saori Sakaue, Asako Sakaue-Sawano, Albin Sandelin, Hiromi Sano, Yuzuru Sasamoto, Hiroki Sato, Alka Saxena, Hideyuki Saya, Andrea Schafferhans, Sebastian Schmeier, Christian Schmidl, Daniel Schmocker, Claudio Schneider, Marcus Schueler, Erik A. Schultes, Gundula Schulze-Tanzil, Colin A. Semple, Shigeto Seno, Wooseok Seo, Jun Sese, Jessica Severin, Guojun Sheng, Jiantao Shi, Yishai Shimoni, Jay W. Shin, Javier SimonSanchez, Asa Sivertsson, Evelina Sjostedt, Cilla Soderhall, Georges St Laurent, Marcus H. Stoiber, Daisuke Sugiyama, Kim M. Summers, Ana Maria Suzuki, Harukazu Suzuki, Kenji Suzuki, Mikiko Suzuki, Naoko Suzuki, Takahiro Suzuki, Douglas J. Swanson, Rolf K. Swoboda, Michihira Tagami, Ayumi Taguchi, Hazuki Takahashi, Masayo Takahashi, Kazuya Takamochi, Satoru Takeda, Yoichi Takenaka, Kin Tung Tam, Hiroshi Tanaka, Rica Tanaka, Yuji Tanaka, Dave Tang, Ichiro Taniuchi, Andrea Tanzer, Hiroshi Tarui, Martin S. Taylor, Aika Terada, Yasuhisa Terao, Alison C. Testa, Mark Thomas, Supat Thongjuea, Kentaro Tomii, Elena Torlai Triglia, Hiroo Toyoda, H. Gwen Tsang, Motokazu Tsujikawa, Mathias Uhlén, Eivind Valen, Marc van de Wetering, Erik van Nimwegen, Dmitry Velmeshev, Roberto Verardo, Morana Vitezic, Kristoffer Vitting-Seerup, Kalle von Feilitzen, Christian R. Voolstra, Ilya E. Vorontsov, Claes Wahlestedt, Wyeth W. Wasserman, Kazuhide Watanabe, Shoko Watanabe, Christine A. Wells, Louise N. Winteringham, Ernst Wolvetang, Haruka Yabukami, Ken Yagi, Takuji Yamada, Yoko Yamaguchi, Masayuki Yamamoto, Yasutomo Yamamoto, Yumiko Yamamoto, Yasunari Yamanaka, Kojiro Yano, Kayoko Yasuzawa, Yukiko Yatsuka, Masahiro Yo, Shunji Yokokura, Misako Yoneda, Emiko Yoshida, Yuki Yoshida, Masahito Yoshihara, Rachel Young, Robert S. Young, Nancy Y. Yu, Noriko Yumoto, Susan E. Zabierowski, Peter G. Zhang, Silvia Zucchelli, Martin Zwahlen, Clément Chatelain, Piero Carninci, Michiel J. L. de Hoon, Wyeth W. Wasserman, Laurent Bréhélin, Charles-Henri Lecellier

  Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism.

  Springer Science and Business Media LLC, Dec. 2021, Nature Communications, 12(1) (1)

  [Refereed]

  Scientific journal


• Enhanced enteric neurogenesis by Schwann cell precursors in mouse models of Hirschsprung disease.

  Toshihiro Uesaka, Mitsumasa Okamoto, Mayumi Nagashimada, Yoshihiro Tsuda, Miho Kihara, Hiroshi Kiyonari, Hideki Enomoto

  Hirschsprung disease (HSCR) is characterized by congenital absence of enteric neurons in distal portions of the gut. Although recent studies identified Schwann cell precursors (SCPs) as a novel cellular source of enteric neurons, it is unknown how SCPs contribute to the disease phenotype of HSCR. Using Schwann cell-specific genetic labeling, we investigated SCP-derived neurogenesis in two mouse models of HSCR; Sox10 haploinsufficient mice exhibiting distal colonic aganglionosis and Ednrb knockout mice showing small intestinal aganglionosis. We also examined Ret dependency in SCP-derived neurogenesis using mice displaying intestinal aganglionosis in which Ret expression was conditionally removed in the Schwann cell lineage. SCP-derived neurons were abundant in the transition zone lying between the ganglionated and aganglionic segments, although SCP-derived neurogenesis was scarce in the aganglionic region. In the transition zone, SCPs mainly gave rise to nitrergic neurons that are rarely observed in the SCP-derived neurons under the normal condition. Enhanced SCP-derived neurogenesis was also detected in the transition zone of mice lacking RET expression in the Schwann cell lineage. Increased SCP-derived neurogenesis in the transition zone suggests that reduction in the vagal neural crest-derived enteric neurons promotes SCP-derived neurogenesis. SCPs may adopt a neuronal subtype by responding to changes in the gut environment. Robust SCP-derived neurogenesis can occur in a Ret-independent manner, which suggests that SCPs are a cellular source to compensate for missing enteric neurons in HSCR.

  Nov. 2021, Glia, 69(11) (11), 2575 - 2590, English, International magazine

  Scientific journal


• Live visualization of a functional RET‐EGFP chimeric receptor in homozygous knock‐in mice

  Mukhamad Sunardi, Keisuke Ito, Hideki Enomoto

  Wiley, Aug. 2021, Development, Growth & Differentiation, 63(6) (6), 285 - 294

  Scientific journal


• Increased RET Activity Coupled with a Reduction in the RET Gene Dosage Causes Intestinal Aganglionosis in Mice

  Mitsumasa Okamoto, Toshihiro Uesaka, Keisuke Ito, Hideki Enomoto

  Society for Neuroscience, May 2021, eneuro, 8(3) (3), ENEURO.0534 - 20.2021

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Point mutagenesis in mouse reveals contrasting pathogenetic effects between MEN2B- and Hirschsprung disease-associated missense mutations of the RET gene.

  Taichi Nakatani, Mitsuhiro Iwasaki, Atsuhiro Yamamichi, Yuta Yoshioka, Toshihiro Uesaka, Yuko Bitoh, Kosaku Maeda, Takumi Fukumoto, Tatsuya Takemoto, Hideki Enomoto

  Missense mutations of the RET gene have been identified in both multiple endocrine neoplasia (MEN) type 2A/B and Hirschsprung disease (HSCR: congenital absence of the enteric nervous system, ENS). Current consensus holds that MEN2A/B and HSCR are caused by activating and inactivating RET mutations, respectively. However, the biological significance of RET missense mutations in vivo has not been fully elucidated. In the present study, we introduced one MEN2B-associated (M918T) and two HSCR-associated (N394K and Y791F) RET missense mutations into the corresponding regions of the mouse Ret gene by genome editing (RetM919T , RetN396K and RetY792F ) and performed histological examinations of Ret-expressing tissues to understand the pathogenetic impact of each mutant in vivo. RetM919T/+ mice displayed MEN2B-related phenotypes, including C-cell hyperplasia and abnormal enlargement of the primary sympathetic ganglia. Similar sympathetic phenotype was observed in RetM919T/- mice, demonstrating a strong pathogenetic effect of the Ret M918T by a single-allele expression. In contrast, no abnormality was found in the ENS of mice harboring the Ret N394K or Y791F mutation. Most surprisingly, single-allele expression of RET N394K or Y791F was sufficient for normal ENS development, indicating that these RET mutants exert largely physiological function in vivo. This study reveals contrasting pathogenetic effects between MEN2B- and HSCR-associated RET missense mutations, and suggests that some of HSCR-associated RET missense mutations are by themselves neither inactivating nor pathogenetic and require involvement of other gene mutations for disease expressivity.

  May 2020, Development, growth & differentiation, 62(4) (4), 214 - 222, English, Domestic magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Generation of conditional ALK F1174L mutant mouse models for the study of neuroblastoma pathogenesis.

  Sachie Ono, Takeshi Saito, Keita Terui, Hideo Yoshida, Hideki Enomoto

  Neuroblastoma, an embryonal tumor arising from the sympathetic ganglia and adrenal medulla, is among the most intractable pediatric cancers. Although a variety of genetic changes have been identified in neuroblastoma, how they contribute to its pathogenesis remains largely unclear. Recent studies have identified alterations of the anaplastic lymphoma kinase (ALK) gene in neuroblastoma; ALK F1174L (a phenylalanine-to-leucine substitution at codon 1174) represents one of the most frequent of these somatic mutations, and is associated with amplification of the MYCN gene, the most reliable marker for the poor survival. We engineered the mouse Alk locus so that ALK F1174L is expressed by its endogenous promoter and can be induced in a spatiotemporally controlled fashion using Cre-loxP system. Although expression of ALK F1174L resulted in enhanced proliferation of sympathetic ganglion progenitors and increased the size of the sympathetic ganglia, it was insufficient to cause neuroblastoma. However, lethal neuroblastoma frequently developed in mice co-expressing ALK F1174L and MYCN, even in a genetic background where MYCN alone does not cause overt tumors. These data reveal that physiological expression of ALK F1174L significantly potentiates the oncogenic ability of MYCN in vivo. Our conditional mutant mice provide a valuable platform for investigating the pathogenesis of neuroblastoma.

  Oct. 2019, Genesis (New York, N.Y. : 2000), 57(10) (10), e23323, English, International magazine

  [Refereed]

  Scientific journal


• Mice conditionally expressing RET(C618F) mutation display C cell hyperplasia and hyperganglionosis of the enteric nervous system.

  Mitsumasa Okamoto, Yuta Yoshioka, Kosaku Maeda, Yuko Bito, Takumi Fukumoto, Toshihiro Uesaka, Hideki Enomoto

  Medullary thyroid carcinoma (MTC) develops from hyperplasia of thyroid C cells and represents one of the major causes of thyroid cancer mortality. Mutations in the cysteine-rich domain (CRD) of the RET gene are the most prevalent genetic cause of MTC. The current consensus holds that such cysteine mutations cause ligand-independent dimerization and constitutive activation of RET. However, given the number of the CRD mutations left uncharacterized, our understanding of the pathogenetic mechanisms by which CRD mutations lead to MTC remains incomplete. We report here that RET(C618F), a mutation identified in MTC patients, displays moderately high basal activity and requires the ligand for its full activation. To assess the biological significance of RET(C618F) in organogenesis, we generated a knock-in mouse line conditionally expressing RET(C618F) cDNA by the Ret promoter. The RET(C618F) allele can be made to be Ret-null and express mCherry by Cre-loxP recombination, which allows the assessment of the biological influence of RET(C618F) in vivo. Mice expressing RET(C618F) display mild C cell hyperplasia and increased numbers of enteric neurons, indicating that RET(C618F) confers gain-of-function phenotypes. This mouse line serves as a novel biological platform for investigating pathogenetic mechanisms involved in MTC and enteric hyperganglionosis.

  May 2019, Genesis (New York, N.Y. : 2000), 57(5) (5), e23292, English, International magazine

  [Refereed]

  Link to Kobe Univ. Repository (Kernel)


• Technologies for Live Imaging of Enteric Neural Crest-Derived Cells.

  Hao MM, Bergner AJ, Newgreen DF, Enomoto H, Young HM

  2019, Methods in molecular biology (Clifton, N.J.), 1976, 97 - 105

  [Refereed]


• Development of the Enteric Nervous System

  Heather M. Young, Lincon A. Stamp, Toshihiro Uesaka, Marlene M. Hao, Donald F. Newgreen, Hideki Enomoto

  Elsevier Inc., Mar. 2018, Physiology of the Gastrointestinal Tract: Sixth Edition, 1-2, 273 - 288, English

  In book


• Dual origin of enteric neurons in vagal Schwann cell precursors and the sympathetic neural crest

  Isabel Espinosa-Medina, Ben Jevans, Franck Boismoreau, Zoubida Chettouh, Hideki Enomoto, Thomas Mueller, Carmen Birchmeier, Alan J. Burns, Jean-Francois Brunet

  Nov. 2017, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 114(45) (45), 11980 - 11985, English

  [Refereed]

  Scientific journal


• Catenins Steer Cell Migration via Stabilization of Front-Rear Polarity

  Vassil Vassilev, Anna Platek, Sylvain Hiver, Hideki Enomoto, Masatoshi Takeichi

  Nov. 2017, DEVELOPMENTAL CELL, 43(4) (4), 463 - +, English

  [Refereed]

  Scientific journal


• FANTOM5 CAGE profiles of human and mouse samples.

  Shuhei Noguchi, Takahiro Arakawa, Shiro Fukuda, Masaaki Furuno, Akira Hasegawa, Fumi Hori, Sachi Ishikawa-Kato, Kaoru Kaida, Ai Kaiho, Mutsumi Kanamori-Katayama, Tsugumi Kawashima, Miki Kojima, Atsutaka Kubosaki, Ri-Ichiroh Manabe, Mitsuyoshi Murata, Sayaka Nagao-Sato, Kenichi Nakazato, Noriko Ninomiya, Hiromi Nishiyori-Sueki, Shohei Noma, Eri Saijyo, Akiko Saka, Mizuho Sakai, Christophe Simon, Naoko Suzuki, Michihira Tagami, Shoko Watanabe, Shigehiro Yoshida, Peter Arner, Richard A Axton, Magda Babina, J Kenneth Baillie, Timothy C Barnett, Anthony G Beckhouse, Antje Blumenthal, Beatrice Bodega, Alessandro Bonetti, James Briggs, Frank Brombacher, Ailsa J Carlisle, Hans C Clevers, Carrie A Davis, Michael Detmar, Taeko Dohi, Albert S B Edge, Matthias Edinger, Anna Ehrlund, Karl Ekwall, Mitsuhiro Endoh, Hideki Enomoto, Afsaneh Eslami, Michela Fagiolini, Lynsey Fairbairn, Mary C Farach-Carson, Geoffrey J Faulkner, Carmelo Ferrai, Malcolm E Fisher, Lesley M Forrester, Rie Fujita, Jun-Ichi Furusawa, Teunis B Geijtenbeek, Thomas Gingeras, Daniel Goldowitz, Sven Guhl, Reto Guler, Stefano Gustincich, Thomas J Ha, Masahide Hamaguchi, Mitsuko Hara, Yuki Hasegawa, Meenhard Herlyn, Peter Heutink, Kelly J Hitchens, David A Hume, Tomokatsu Ikawa, Yuri Ishizu, Chieko Kai, Hiroshi Kawamoto, Yuki I Kawamura, Judith S Kempfle, Tony J Kenna, Juha Kere, Levon M Khachigian, Toshio Kitamura, Sarah Klein, S Peter Klinken, Alan J Knox, Soichi Kojima, Haruhiko Koseki, Shigeo Koyasu, Weonju Lee, Andreas Lennartsson, Alan Mackay-Sim, Niklas Mejhert, Yosuke Mizuno, Hiromasa Morikawa, Mitsuru Morimoto, Kazuyo Moro, Kelly J Morris, Hozumi Motohashi, Christine L Mummery, Yutaka Nakachi, Fumio Nakahara, Toshiyuki Nakamura, Yukio Nakamura, Tadasuke Nozaki, Soichi Ogishima, Naganari Ohkura, Hiroshi Ohno, Mitsuhiro Ohshima, Mariko Okada-Hatakeyama, Yasushi Okazaki, Valerio Orlando, Dmitry A Ovchinnikov, Robert Passier, Margaret Patrikakis, Ana Pombo, Swati Pradhan-Bhatt, Xian-Yang Qin, Michael Rehli, Patrizia Rizzu, Sugata Roy, Antti Sajantila, Shimon Sakaguchi, Hiroki Sato, Hironori Satoh, Suzana Savvi, Alka Saxena, Christian Schmidl, Claudio Schneider, Gundula G Schulze-Tanzil, Anita Schwegmann, Guojun Sheng, Jay W Shin, Daisuke Sugiyama, Takaaki Sugiyama, Kim M Summers, Naoko Takahashi, Jun Takai, Hiroshi Tanaka, Hideki Tatsukawa, Andru Tomoiu, Hiroo Toyoda, Marc van de Wetering, Linda M van den Berg, Roberto Verardo, Dipti Vijayan, Christine A Wells, Louise N Winteringham, Ernst Wolvetang, Yoko Yamaguchi, Masayuki Yamamoto, Chiyo Yanagi-Mizuochi, Misako Yoneda, Yohei Yonekura, Peter G Zhang, Silvia Zucchelli, Imad Abugessaisa, Erik Arner, Jayson Harshbarger, Atsushi Kondo, Timo Lassmann, Marina Lizio, Serkan Sahin, Thierry Sengstag, Jessica Severin, Hisashi Shimoji, Masanori Suzuki, Harukazu Suzuki, Jun Kawai, Naoto Kondo, Masayoshi Itoh, Carsten O Daub, Takeya Kasukawa, Hideya Kawaji, Piero Carninci, Alistair R R Forrest, Yoshihide Hayashizaki

  In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE (Cap Analysis of Gene Expression) coupled with single-molecule sequencing. Approximately three thousands of samples, consisting of a variety of primary cells, tissues, cell lines, and time series samples during cell activation and development, were subjected to a uniform pipeline of CAGE data production. The analysis pipeline started by measuring RNA extracts to assess their quality, and continued to CAGE library production by using a robotic or a manual workflow, single molecule sequencing, and computational processing to generate frequencies of transcription initiation. Resulting data represents the consequence of transcriptional regulation in each analyzed state of mammalian cells. Non-overlapping peaks over the CAGE profiles, approximately 200,000 and 150,000 peaks for the human and mouse genomes, were identified and annotated to provide precise location of known promoters as well as novel ones, and to quantify their activities.

  Aug. 2017, Scientific data, 4, 170112 - 170112, English, International magazine

  [Refereed]

  Scientific journal


• Striatal hypodopamine phenotypes found in transgenic mice that overexpress glial cell line-derived neurotrophic factor

  Hidekazu Sotoyama, Yuriko Iwakura, Kanako Oda, Toshikuni Sasaoka, Nobuyuki Takei, Akiyoshi Kakita, Hideki Enomoto, Hiroyuki Nawa

  Jul. 2017, NEUROSCIENCE LETTERS, 654, 99 - 106, English

  [Refereed]

  Scientific journal


• The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome

  Laurence D. Hurst, Avazeh T. Ghanbarian, Alistair R. R. Forrest, FANTOM consortium, Lukasz Huminiecki, Michael Rehli, J. Kenneth Baillie, Michiel J. L. de Hoon, Vanja Haberle, Timo Lassmann, Ivan V. Kulakovskiy, Marina Lizio, Masayoshi Itoh, Robin Andersson, Christopher J. Mungall, Terrence F. Meehan, Sebastian Schmeier, Nicolas Bertin, Mette Jørgensen, Emmanuel Dimont, Erik Arner, Christian Schmidl, Ulf Schaefer, Yulia A. Medvedeva, Charles Plessy, Morana Vitezic, Jessica Severin, Colin A. Semple, Yuri Ishizu, Robert S. Young, Margherita Francescatto, Intikhab Alam, Davide Albanese, Gabriel M. Altschuler, Takahiro Arakawa, John A.C. Archer, Peter Arner, Magda Babina, Sarah Baker, Piotr J. Balwierz, Anthony G. Beckhouse, Swati-Bhatt Pradhan, Judith A. Blake, Antje Blumenthal, Beatrice Bodega, Alessandro Bonetti, James Briggs, Frank Brombacher, A. Maxwell Burroughs, Andrea Califano, Carlo V. Cannistraci, Daniel Carbajo, Yun Chen, Marco Chierici, Yari Ciani, Hans C. Clevers, Emiliano Dalla, Carrie A. Davis, Michael Detmar, Alexander D. Diehl, Taeko Dohi, Finn Drabløs, Albert S.B. Edge, Matthias Edinger, Karl Ekwall, Mitsuhiro Endoh, Hideki Enomoto, Michela Fagiolini, Lynsey Fairbairn, Hai Fang, Mary C. Farach-Carson, Geoffrey J. Faulkner, Alexander V. Favorov, Malcolm E. Fisher, Martin C. Frith, Rie Fujita, Shiro Fukuda, Cesare Furlanello, Masaaki Furuno, Jun-ichi Furusawa, Teunis B. Geijtenbeek, Andrew Gibson, Thomas Gingeras, Daniel Goldowitz, Julian Gough, Sven Guhl, Reto Guler, Stefano Gustincich, Thomas J. Ha, Masahide Hamaguchi, Mitsuko Hara, Matthias Harbers, Jayson Harshbarger, Akira Hasegawa, Yuki Hasegawa, Takehiro Hashimoto, Meenhard Herlyn, Kelly J. Hitchens, Shannan J. Ho Sui, Oliver M. Hofmann, Ilka Hoof, Fumi Hori, Lukasz Huminiecki, Kei Iida, Tomokatsu Ikawa, Boris R. Jankovic, Hui Jia, Anagha Joshi, Giuseppe Jurman, Bogumil Kaczkowski, Chieko Kai, Kaoru Kaida, Ai Kaiho, Kazuhiro Kajiyama, Mutsumi-Katayama Kanamori, Artem S. Kasianov, Takeya Kasukawa, Shintaro Katayama, Sachi Kato, Shuji Kawaguchi, Hiroshi Kawamoto, Yuki I. Kawamura, Tsugumi Kawashima, Judith S. Kempfle, Tony J. Kenna, Juha Kere, Levon M. Khachigian, Toshio Kitamura, S. Peter Klinken, Alan J. Knox, Miki Kojima, Soichi Kojima, Naoto Kondo, Haruhiko Koseki, Shigeo Koyasu, Sarah Krampitz, Atsutaka Kubosaki, Andrew T. Kwon, Jeroen F.J. Laros, Weonju Lee, Andreas Lennartsson, Kang Li, Berit Lilje, Leonard Lipovich, Alan-sim Mackay, Riichiroh Manabe, Jessica C. Mar, Benoit Marchand, Anthony Mathelier, Niklas Mejhert, Alison Meynert, Yosuke Mizuno, David A. de Lima Morais, Hiromasa Morikawa, Mitsuru Morimoto, Kazuyo Moro, Efthymios Motakis, Hozumi Motohashi, Christine L. Mummery, Mitsuyoshi Murata, Sayaka-Sato Nagao, Yutaka Nakachi, Fumio Nakahara, Toshiyuki Nakamura, Yukio Nakamura, Kenichi Nakazato, Erik van Nimwegen, Noriko Ninomiya, Hiromi Nishiyori, Shohei Noma, Tadasuke Nozaki, Soichi Ogishima, Naganari Ohkura, Hiroko Ohmiya, Hiroshi Ohno, Mitsuhiro Ohshima, Mariko-Hatakeyama Okada, Yasushi Okazaki, Valerio Orlando, Dmitry A. Ovchinnikov, Arnab Pain, Robert Passier, Margaret Patrikakis, Helena Persson, Silvano Piazza, James G.D. Prendergast, Owen J.L. Rackham, Jordan A. Ramilowski, Mamoon Rashid, Timothy Ravasi, Patrizia Rizzu, Marco Roncador, Sugata Roy, Morten B. Rye, Eri Saijyo, Antti Sajantila, Akiko Saka, Shimon Sakaguchi, Mizuho Sakai, Hiroki Sato, Hironori Satoh, Suzana Savvi, Alka Saxena, Claudio Schneider, Erik A. Schultes, Gundula G. Schulze-Tanzil, Anita Schwegmann, Thierry Sengstag, Guojun Sheng, Hisashi Shimoji, Yishai Shimoni, Jay W. Shin, Christophe Simon, Daisuke Sugiyama, Takaaki Sugiyama, Masanori Suzuki, Naoko Suzuki, Rolf K. Swoboda, Peter A.C. 't Hoen, Michihira Tagami, Naoko Takahashi, Jun Takai, Hiroshi Tanaka, Hideki Tatsukawa, Zuotian Tatum, Mark Thompson, Hiroo Toyoda, Tetsuro Toyoda, Eivind Valen, Marc van de Wetering, Linda M. van den Berg, Roberto Verardo, Dipti Vijayan, Ilya E. Vorontsov, Wyeth W. Wasserman, Shoko Watanabe, Christine A. Wells, Louise N. Winteringham, Ernst Wolvetang, Emily J. Wood, Yoko Yamaguchi, Masayuki Yamamoto, Misako Yoneda, Yohei Yonekura, Shigehiro Yoshida, Suzan E. Zabierowski, Peter G. Zhang, Xiaobei Zhao, Silvia Zucchelli, Kim M. Summers, Harukazu Suzuki, Carsten O. Daub, Jun Kawai, Peter Heutink, Winston Hide, Tom C. Freeman, Boris Lenhard, Vladimir B. Bajic, Martin S. Taylor, Vsevolod J. Makeev, Albin Sandelin, David A. Hume, Piero Carninci, Yoshihide Hayashizaki

  Public Library of Science, Dec. 2015, PLoS Biology, 13(12) (12), English

  [Refereed]

  Scientific journal


• Neuronal Differentiation in Schwann Cell Lineage Underlies Postnatal Neurogenesis in the Enteric Nervous System

  Toshihiro Uesaka, Mayumi Nagashimada, Hideki Enomoto

  Jul. 2015, JOURNAL OF NEUROSCIENCE, 35(27) (27), 9879 - 9888, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• The neurotrophic factor receptor RET drives haematopoietic stem cell survival and function

  Diogo Fonseca-Pereira, Silvia Arroz-Madeira, mariana Rodrigues-Campos, Ines A. M. Barbosa, Rita G. Domingues, Teresa Bento, Afonso R. M. Almeida, Helder Ribeiro, Alexandre J. Potocnik, Hideki Enomoto, Henrique Veiga-Fernandes

  Oct. 2014, NATURE, 514(7520) (7520), 98 - +, English

  [Refereed]

  Scientific journal


• Mouse Spermatogenic Stem Cells Continually Interconvert between Equipotent Singly Isolated and Syncytial States

  Kenshiro Hara, Toshinori Nakagawa, Hideki Enomoto, Mikiko Suzuki, Masayuki Yamamoto, Benjamin D. Simons, Shosei Yoshida

  May 2014, CELL STEM CELL, 14(5) (5), 658 - 672, English

  [Refereed]

  Scientific journal


• Differential roles of epigenetic changes and Foxp3 expression in regulatory T cell-specific transcriptional regulation

  Hiromasa Morikawa, Naganari Ohkura, Alexis Vandenbon, Masayoshi Itoh, Sayaka Nagao-Sato, Hideya Kawaji, Timo Lassmann, Piero Carninci, Yoshihide Hayashizaki, Alistair R. R. Forrest, Daron M. Standley, Hiroshi Date, Shimon Sakaguchi

  Apr. 2014, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 111(14) (14), 5289 - 5294, English

  [Refereed]

  Scientific journal


• A promoter-level mammalian expression atlas.

  Alistair R R Forrest, Hideya Kawaji, Michael Rehli, J Kenneth Baillie, Michiel J L de Hoon, Vanja Haberle, Timo Lassmann, Ivan V Kulakovskiy, Marina Lizio, Masayoshi Itoh, Robin Andersson, Christopher J Mungall, Terrence F Meehan, Sebastian Schmeier, Nicolas Bertin, Mette Jørgensen, Emmanuel Dimont, Erik Arner, Christian Schmidl, Ulf Schaefer, Yulia A Medvedeva, Charles Plessy, Morana Vitezic, Jessica Severin, Colin A Semple, Yuri Ishizu, Robert S Young, Margherita Francescatto, Intikhab Alam, Davide Albanese, Gabriel M Altschuler, Takahiro Arakawa, John A C Archer, Peter Arner, Magda Babina, Sarah Rennie, Piotr J Balwierz, Anthony G Beckhouse, Swati Pradhan-Bhatt, Judith A Blake, Antje Blumenthal, Beatrice Bodega, Alessandro Bonetti, James Briggs, Frank Brombacher, A Maxwell Burroughs, Andrea Califano, Carlo V Cannistraci, Daniel Carbajo, Yun Chen, Marco Chierici, Yari Ciani, Hans C Clevers, Emiliano Dalla, Carrie A Davis, Michael Detmar, Alexander D Diehl, Taeko Dohi, Finn Drabløs, Albert S B Edge, Matthias Edinger, Karl Ekwall, Mitsuhiro Endoh, Hideki Enomoto, Michela Fagiolini, Lynsey Fairbairn, Hai Fang, Mary C Farach-Carson, Geoffrey J Faulkner, Alexander V Favorov, Malcolm E Fisher, Martin C Frith, Rie Fujita, Shiro Fukuda, Cesare Furlanello, Masaaki Furino, Jun-ichi Furusawa, Teunis B Geijtenbeek, Andrew P Gibson, Thomas Gingeras, Daniel Goldowitz, Julian Gough, Sven Guhl, Reto Guler, Stefano Gustincich, Thomas J Ha, Masahide Hamaguchi, Mitsuko Hara, Matthias Harbers, Jayson Harshbarger, Akira Hasegawa, Yuki Hasegawa, Takehiro Hashimoto, Meenhard Herlyn, Kelly J Hitchens, Shannan J Ho Sui, Oliver M Hofmann, Ilka Hoof, Furni Hori, Lukasz Huminiecki, Kei Iida, Tomokatsu Ikawa, Boris R Jankovic, Hui Jia, Anagha Joshi, Giuseppe Jurman, Bogumil Kaczkowski, Chieko Kai, Kaoru Kaida, Ai Kaiho, Kazuhiro Kajiyama, Mutsumi Kanamori-Katayama, Artem S Kasianov, Takeya Kasukawa, Shintaro Katayama, Sachi Kato, Shuji Kawaguchi, Hiroshi Kawamoto, Yuki I Kawamura, Tsugumi Kawashima, Judith S Kempfle, Tony J Kenna, Juha Kere, Levon M Khachigian, Toshio Kitamura, S Peter Klinken, Alan J Knox, Miki Kojima, Soichi Kojima, Naoto Kondo, Haruhiko Koseki, Shigeo Koyasu, Sarah Krampitz, Atsutaka Kubosaki, Andrew T Kwon, Jeroen F J Laros, Weonju Lee, Andreas Lennartsson, Kang Li, Berit Lilje, Leonard Lipovich, Alan Mackay-Sim, Ri-ichiroh Manabe, Jessica C Mar, Benoit Marchand, Anthony Mathelier, Niklas Mejhert, Alison Meynert, Yosuke Mizuno, David A de Lima Morais, Hiromasa Morikawa, Mitsuru Morimoto, Kazuyo Moro, Efthymios Motakis, Hozumi Motohashi, Christine L Mummery, Mitsuyoshi Murata, Sayaka Nagao-Sato, Yutaka Nakachi, Fumio Nakahara, Toshiyuki Nakamura, Yukio Nakamura, Kenichi Nakazato, Erik van Nimwegen, Noriko Ninomiya, Hiromi Nishiyori, Shohei Noma, Shohei Noma, Tadasuke Noazaki, Soichi Ogishima, Naganari Ohkura, Hiroko Ohimiya, Hiroshi Ohno, Mitsuhiro Ohshima, Mariko Okada-Hatakeyama, Yasushi Okazaki, Valerio Orlando, Dmitry A Ovchinnikov, Arnab Pain, Robert Passier, Margaret Patrikakis, Helena Persson, Silvano Piazza, James G D Prendergast, Owen J L Rackham, Jordan A Ramilowski, Mamoon Rashid, Timothy Ravasi, Patrizia Rizzu, Marco Roncador, Sugata Roy, Morten B Rye, Eri Saijyo, Antti Sajantila, Akiko Saka, Shimon Sakaguchi, Mizuho Sakai, Hiroki Sato, Suzana Savvi, Alka Saxena, Claudio Schneider, Erik A Schultes, Gundula G Schulze-Tanzil, Anita Schwegmann, Thierry Sengstag, Guojun Sheng, Hisashi Shimoji, Yishai Shimoni, Jay W Shin, Christophe Simon, Daisuke Sugiyama, Takaai Sugiyama, Masanori Suzuki, Naoko Suzuki, Rolf K Swoboda, Peter A C 't Hoen, Michihira Tagami, Naoko Takahashi, Jun Takai, Hiroshi Tanaka, Hideki Tatsukawa, Zuotian Tatum, Mark Thompson, Hiroo Toyodo, Tetsuro Toyoda, Elvind Valen, Marc van de Wetering, Linda M van den Berg, Roberto Verado, Dipti Vijayan, Ilya E Vorontsov, Wyeth W Wasserman, Shoko Watanabe, Christine A Wells, Louise N Winteringham, Ernst Wolvetang, Emily J Wood, Yoko Yamaguchi, Masayuki Yamamoto, Misako Yoneda, Yohei Yonekura, Shigehiro Yoshida, Susan E Zabierowski, Peter G Zhang, Xiaobei Zhao, Silvia Zucchelli, Kim M Summers, Harukazu Suzuki, Carsten O Daub, Jun Kawai, Peter Heutink, Winston Hide, Tom C Freeman, Boris Lenhard, Vladimir B Bajic, Martin S Taylor, Vsevolod J Makeev, Albin Sandelin, David A Hume, Piero Carninci, Yoshihide Hayashizaki

  Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly 'housekeeping', whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.

  Mar. 2014, Nature, 507(7493) (7493), 462 - 70, English, International magazine

  [Refereed]

  Scientific journal


• Colonizing while migrating: how do individual enteric neural crest cells behave?

  Heather M. Young, Annette J. Bergner, Matthew J. Simpson, Sonja J. McKeown, Marlene M. Hao, Colin R. Anderson, Hideki Enomoto

  Mar. 2014, BMC BIOLOGY, 12, 23, English

  [Refereed]

  Scientific journal


• Tissue Interactions in Neural Crest Cell Development and Disease

  Yoshiko Takahashi, Douglas Sipp, Hideki Enomoto

  Aug. 2013, SCIENCE, 341(6148) (6148), 860 - 863, English

  [Refereed]

  Scientific journal


• Proliferation and Cell Cycle Dynamics in the Developing Stellate Ganglion

  David G. Gonsalvez, Kylie N. Cane, Kerry A. Landman, Hideki Enomoto, Heather M. Young, Colin R. Anderson

  Apr. 2013, JOURNAL OF NEUROSCIENCE, 33(14) (14), 5969 - 5979, English

  [Refereed]

  Scientific journal


• GDNF and endothelin 3 regulate migration of enteric neural crest-derived cells via protein kinase A and Rac1

  Akihiro Goto, Kenta Sumiyama, Yuji Kamioka, Eiji Nakasyo, Keisuke Ito, Mitsuhiro Iwasaki, Hideki Enomoto, Michiyuki Matsuda

  Mar. 2013, Journal of Neuroscience, 33(11) (11), 4901 - 4912, English

  [Refereed]

  Scientific journal


• Transplanted progenitors generate functional enteric neurons in the postnatal colon

  Ryo Hotta, Lincon A. Stamp, Jaime P.P. Foong, Sophie N. McConnell, Annette J. Bergner, Richard B. Anderson, Hideki Enomoto, Donald F. Newgreen, Florian Obermayr, John B. Furness, Heather M. Young

  Mar. 2013, Journal of Clinical Investigation, 123(3) (3), 1182 - 1191, English

  [Refereed]

  Scientific journal


• Development and developmental disorders of the enteric nervous system

  Florian Obermayr, Ryo Hotta, Hideki Enomoto, Heather M. Young

  Jan. 2013, NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY, 10(1) (1), 43 - 57, English

  [Refereed]

  Scientific journal


• GDNF signaling levels control migration and neuronal differentiation of enteric ganglion precursors

  Toshihiro Uesaka, Mayumi Nagashimada, Hideki Enomoto

  Society for Neuroscience, 2013, Journal of Neuroscience, 33(41) (41), 16372 - 16382, English

  [Refereed]

  Scientific journal


• Trans-mesenteric neural crest cells are the principal source of the colonic enteric nervous system

  Chihiro Nishiyama, Toshihiro Uesaka, Takayuki Manabe, Yohei Yonekura, Takashi Nagasawa, Donald F. Newgreen, Heather M. Young, Hideki Enomoto

  Sep. 2012, NATURE NEUROSCIENCE, 15(9) (9), 1211 - U64, English

  [Refereed]

  Scientific journal


• Autonomic neurocristopathy-associated mutations in PHOX2B dysregulate Sox10 expression

  Mayumi Nagashimada, Hiroshi Ohta, Chong Li, Kazuki Nakao, Toshihiro Uesaka, Jean-Francois Brunet, Jeanne Amiel, Delphine Trochet, Teruhiko Wakayama, Hideki Enomoto

  Sep. 2012, JOURNAL OF CLINICAL INVESTIGATION, 122(9) (9), 3145 - 3158, English

  [Refereed]

  Scientific journal


• Prox1 postmitotically defines dentate gyrus cells by specifying granule cell identity over CA3 pyramidal cell fate in the hippocampus

  Tomohiko Iwano, Aki Masuda, Hiroshi Kiyonari, Hideki Enomoto, Fumio Matsuzaki

  Aug. 2012, DEVELOPMENT, 139(16) (16), 3051 - 3062, English

  [Refereed]

  Scientific journal


• Differential RET Signaling Pathways Drive Development of the Enteric Lymphoid and Nervous Systems

  Amisha Patel, Nicola Harker, Lara Moreira-Santos, Manuela Ferreira, Kieran Alden, Jon Timmis, Katie Foster, Anna Garefalaki, Panayotis Pachnis, Paul Andrews, Hideki Enomoto, Jeffrey Milbrandt, Vassilis Pachnis, Mark C. Coles, Dimitris Kioussis, Henrique Veiga-Fernandes

  Jul. 2012, SCIENCE SIGNALING, 5(235) (235), ra55, English

  [Refereed]

  Scientific journal


• Development of the Enteric Nervous System

  Heather M. Young, Donald F. Newgreen, Hideki Enomoto

  Elsevier Inc., 2012, Physiology of the Gastrointestinal Tract, 1, 475 - 488, English

  [Refereed]

  In book


• Neural Precursor Death Is Central to the Pathogenesis of Intestinal Aganglionosis in Ret Hypomorphic Mice

  Toshihiro Uesaka, Hideki Enomoto

  Apr. 2010, JOURNAL OF NEUROSCIENCE, 30(15) (15), 5211 - 5218, English

  [Refereed]

  Scientific journal


• RET Signaling Is Required for Survival and Normal Function of Nonpeptidergic Nociceptors

  Judith P. Golden, Masato Hoshi, Mohammed A. Nassar, Hideki Enomoto, John N. Wood, Jeffrey Milbrandt, Robert W. Gereau, Eugene M. Johnson, Sanjay Jain

  Mar. 2010, JOURNAL OF NEUROSCIENCE, 30(11) (11), 3983 - 3994, English

  [Refereed]

  Scientific journal


• Molecular Identification of Rapidly Adapting Mechanoreceptors and Their Developmental Dependence on Ret Signaling

  Wenqin Luo, Hideki Enomoto, Frank L. Rice, Jeffrey Milbrandt, David D. Ginty

  Dec. 2009, NEURON, 64(6) (6), 841 - 856, English

  [Refereed]

  Scientific journal


• Ret-Dependent Cell Rearrangements in the Wolffian Duct Epithelium Initiate Ureteric Bud Morphogenesis

  Xuan Chi, Odysse Michos, Reena Shakya, Paul Riccio, Hideki Enomoto, Jonathan D. Licht, Naoya Asai, Masahide Takahashi, Nobutaka Ohgami, Masashi Kato, Cathy Mendelsohn, Frank Costantini

  Aug. 2009, DEVELOPMENTAL CELL, 17(2) (2), 199 - 209, English

  [Refereed]

  Scientific journal


• Regionalized Loss of Parvalbumin Interneurons in the Cerebral Cortex of Mice with Deficits in GFR alpha 1 Signaling

  Alison J. Canty, Jule Dietze, Michael Harvey, Hideki Enomoto, Jeffrey Milbrandt, Carlos F. Ibanez

  Aug. 2009, JOURNAL OF NEUROSCIENCE, 29(34) (34), 10695 - 10705, English

  [Refereed]

  Scientific journal


• Development of satellite glia in mouse sympathetic ganglia: Gdnf and Gfr alpha 1 are not essential

  Thomas Callahan, Heather M. Young, Richard B. Anderson, Hideki Enomoto, Colin R. Anderson

  Oct. 2008, GLIA, 56(13) (13), 1428 - 1437, English

  [Refereed]

  Scientific journal


• Diminished Ret expression compromises neuronal survival in the colon and causes intestinal aganglionosis in mice

  Toshihiro Uesaka, Mayumi Nagashimada, Shigenobu Yonemura, Hideki Enomoto

  May 2008, JOURNAL OF CLINICAL INVESTIGATION, 118(5) (5), 1890 - 1898, English

  [Refereed]

  Scientific journal


• The neurotrophic effects of glial cell line-derived neurotrophic factor on spinal motoneurons are restricted to fusimotor subtypes

  Thomas W. Gould, Shigenobu Yonemura, Ronald W. Oppenheim, Shiho Ohmori, Hideki Enomoto

  Feb. 2008, JOURNAL OF NEUROSCIENCE, 28(9) (9), 2131 - 2146, English

  [Refereed]

  Scientific journal


• Conditional ablation of GFR alpha 1 in postmigratory enteric neurons triggers unconventional neuronal death in the colon and causes a Hirschsprung's disease phenotype

  Toshihiro Uesaka, Sanjay Jain, Shigenobu Yonemura, Yasuo Uchiyama, Jeffrey Milbrandt, Hideki Enomoto

  Jun. 2007, DEVELOPMENT, 134(11) (11), 2171 - 2181, English

  [Refereed]

  Scientific journal


• Differential gene expression and functional analysis implicate novel mechanisms in enteric nervous system precursor migration and neuritogenesis

  Bhupinder P. S. Vohra, Keiji Tsuji, Mayumi Nagashimada, Toshihiro Uesaka, Daniel Wind, Ming Fu, Jennifer Armon, Hideki Enomoto, Robert O. Heuckeroth

  Oct. 2006, DEVELOPMENTAL BIOLOGY, 298(1) (1), 259 - 271, English

  [Refereed]

  Scientific journal


• GFR alpha 1 expression in cells lacking RET is dispensable for organogenesis and nerve regeneration

  H Enomoto, Hughes, I, J Golden, RH Baloh, S Yonemura, RO Heuckeroth, EM Johnson, J Milbrandt

  Nov. 2004, NEURON, 44(4) (4), 623 - 636, English

  [Refereed]

  Scientific journal


• The enteric nervous system is not essential for the propulsion of gut contents in fetal mice

  RB Anderson, H Enomoto, JC Bornstein, HM Young

  Oct. 2004, GUT, 53(10) (10), 1546 - 1547, English

  [Refereed]

  Scientific journal


• Dok-6, a novel p62 Dok family member, promotes Ret-mediated neurite outgrowth

  RJ Crowder, H Enomoto, M Yang, EM Johnson, J Milbrandt

  Oct. 2004, JOURNAL OF BIOLOGICAL CHEMISTRY, 279(40) (40), 42072 - 42081, English

  [Refereed]

  Scientific journal


• Neural cells in the esophagus respond to glial cell line-derived neurotrophic factor and neurturin, and are RET-dependent

  H Yan, AJ Bergner, H Enomoto, J Milbrandt, DF Newgreen, HM Young

  Aug. 2004, DEVELOPMENTAL BIOLOGY, 272(1) (1), 118 - 133, English

  [Refereed]

  Scientific journal


• Dynamics of neural crest-derived cell migration in the embryonic mouse gut

  HM Young, AJ Bergner, RB Anderson, H Enomoto, J Milbrandt, DF Newgreen, PM Whitington

  Jun. 2004, DEVELOPMENTAL BIOLOGY, 270(2) (2), 455 - 473, English

  [Refereed]

  Scientific journal


• GDNF availability determines enteric neuron number by controlling precursor proliferation

  S Gianino, Grider, JR, J Cresswell, H Enomoto, RO Heuckeroth

  May 2003, DEVELOPMENT, 130(10) (10), 2187 - 2198, English

  [Refereed]

  Scientific journal


• RET signaling is essential for migration, axonal growth and axon guidance of developing sympathetic neurons

  H Enomoto, PA Crawford, A Gorodinsky, RO Heuckeroth, EM Johnson, J Milbrandt

  Oct. 2001, DEVELOPMENT, 128(20) (20), 3963 - 3974, English

  [Refereed]

  Scientific journal


• Development of cranial parasympathetic ganglia requires sequential actions of GDNF and neurturin

  H Enomoto, RO Heuckeroth, JP Golden, EM Johnson, J Milbrandt

  Nov. 2000, DEVELOPMENT, 127(22) (22), 4877 - 4889, English

  [Refereed]

  Scientific journal


• Dual fluorescent in situ hybridization and immunohistochemical detection with tyramide signal amplification

  AU Zaidi, H Enomoto, J Milbrandt, KA Roth

  Oct. 2000, JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 48(10) (10), 1369 - 1375, English

  [Refereed]

  Scientific journal


• Gene targeting reveals a critical role for neurturin in the development and maintenance of enteric, sensory, and parasympathetic neurons

  RO Heuckeroth, H Enomoto, Grider, JR, JP Golden, JA Hanke, A Jackman, DC Molliver, ME Bardgett, WD Snider, EM Johnson, J Milbrandt

  Feb. 1999, NEURON, 22(2) (2), 253 - 263, English

  [Refereed]

  Scientific journal


• Expression of MRP and cMOAT in childhood neuroblastomas and malignant liver tumors and its relevance to clinical behavior

  T Matsunaga, H Shirasawa, T Hishiki, H Enomoto, K Kouchi, Y Ohtsuka, J Iwai, H Yoshida, M Tanabe, S Kobayashi, T Asano, T Etoh, Y Nishi, N Ohnuma

  Dec. 1998, JAPANESE JOURNAL OF CANCER RESEARCH, 89(12) (12), 1276 - 1283, English

  [Refereed]

  Scientific journal


• Artemin, a novel member of the GDNF ligand family, supports peripheral and central neurons and signals through the GFR alpha 3-RET receptor complex

  RH Baloh, MG Tansey, PA Lampe, TJ Fahrner, H Enomoto, KS Simburger, ML Leitner, T Araki, EM Johnson, J Milbrandt

  Dec. 1998, NEURON, 21(6) (6), 1291 - 1302, English

  [Refereed]

  Scientific journal


• In vivo karyotypic evolution with altered biological characteristics in a case of neuroblastoma

  H Enomoto, Y Nakamura, K Kondo, M Hirose, Y Kaneko, H Horie, H Takahashi, N Ohnuma, M Tanabe, A Nakagawara

  Sep. 1998, JOURNAL OF PEDIATRIC SURGERY, 33(9) (9), 1404 - 1407, English

  [Refereed]

  Scientific journal


• GFR alpha 1-deficient mice have deficits in the enteric nervous system and kidneys

  H Enomoto, T Araki, A Jackman, RO Heuckeroth, WD Snider, EM Johnson, J Milbrandt

  Aug. 1998, NEURON, 21(2) (2), 317 - 324, English

  [Refereed]

  Scientific journal


• Antitumor vaccine effect of irradiated murine neuroblastoma cells producing interleukin-2 or granulocyte macrophage-colony stimulating factor

  H Yoshida, H Enomoto, K Kawamura, K Takenaga, M Tanabe, N Ohnuma, S Sakiyama, M Tagawa

  Jul. 1998, INTERNATIONAL JOURNAL OF ONCOLOGY, 13(1) (1), 73 - 78, English

  [Refereed]

  Scientific journal


• Neuronal src and trk a protooncogene expression in neuroblastomas and patient prognosis

  T Matsunaga, H Shirasawa, H Enomoto, H Yoshida, J Iwai, M Tanabe, K Kawamura, T Etoh, N Ohnuma

  Jun. 1998, INTERNATIONAL JOURNAL OF CANCER, 79(3) (3), 226 - 231, English

  [Refereed]

  Scientific journal


• Impaired tumorigenicity of IL-4-producing murine neuroblastoma cells in immunodeficient nude mice

  H Yoshida, H Enomoto, M Miyauchi, K Takenaga, M Tanabe, N Ohnuma, S Sakiyama, M Tagawa

  May 1998, INTERNATIONAL JOURNAL OF ONCOLOGY, 12(5) (5), 1067 - 1071, English

  [Refereed]

  Scientific journal


• Impaired tumorigenicity and decreased liver metastasis of murine neuroblastoma cells engineered to secrete interleukin-2 or granulocyte macrophage colony-stimulating factor

  H Yoshida, H Enomoto, M Tagawa, K Takenaga, K Tasaki, A Nakagawara, N Ohnuma, H Takahashi, S Sakiyama

  Mar. 1998, CANCER GENE THERAPY, 5(2) (2), 67 - 73, English

  [Refereed]

  Scientific journal


• B80 RNA-PCRによる神経特異的src, trk A, Ha-rasの発現と神経芽腫の予後

  松永 正訓, 田辺 政裕, 吉田 英生, 岩井 潤, 榎本 秀樹, 吉野 薫, 大塚 恭寛, 幸地 克憲, 岡田 忠雄, 川村 健児, 江東 孝夫, 大沼 直躬

  特定非営利活動法人 日本小児外科学会, 1998, 日本小児外科学会雑誌, 34(3) (3), 697 - 697, Japanese


• The genomic analysis of human DAN gene

  T Ozaki, H Enomoto, Y Nakamura, K Kondo, N Seki, M Ohira, N Nomura, M Ohki, A Nakagawara, S Sakiyama

  Sep. 1997, DNA AND CELL BIOLOGY, 16(9) (9), 1031 - 1039, English

  [Refereed]

  Scientific journal


• Chromosome mapping of the mouse and rat homologs of the human DAN gene, D1S1733E

  Y Matsuda, T Ozaki, H Enomoto, T Saito, S Sakiyama

  Sep. 1996, MAMMALIAN GENOME, 7(9) (9), 709 - 710, English

  [Refereed]

  Scientific journal


• A REGION OF CONSISTENT DELETION IN NEUROBLASTOMA MAPS WITHIN HUMAN-CHROMOSOME 1P36.2-36.3

  PS WHITE, JM MARIS, C BELTINGER, E SULMAN, HN MARSHALL, M FUJIMORI, BA KAUFMAN, JA BIEGEL, C ALLEN, C HILLARD, MB VALENTINE, AT LOOK, H ENOMOTO, S SAKIYAMA, GM BRODEUR

  Jun. 1995, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 92(12) (12), 5520 - 5524, English

  [Refereed]

  Scientific journal


• OVEREXPRESSION OF DAN GENE-PRODUCT IN NORMAL RAT FIBROBLASTS CAUSES A RETARDATION OF THE ENTRY INTO THE S-PHASE

  T OZAKI, Y NAKAMURA, H ENOMOTO, M HIROSE, S SAKIYAMA

  Feb. 1995, CANCER RESEARCH, 55(4) (4), 895 - 900, English

  [Refereed]

  Scientific journal


• IDENTIFICATION OF HUMAN DAN GENE, MAPPING TO THE PUTATIVE NEUROBLASTOMA TUMOR-SUPPRESSOR LOCUS

  H ENOMOTO, T OZAKI, E TAKAHASHI, N NOMURA, S TABATA, H TAKAHASHI, N OHNUMA, M TANABE, J IWAI, H YOSHIDA, T MATSUNAGA, S SAKIYAMA

  Oct. 1994, ONCOGENE, 9(10) (10), 2785 - 2791, English

  [Refereed]

  Scientific journal


• COMPLEX-FORMATION BETWEEN LAMIN-A AND THE RETINOBLASTOMA GENE-PRODUCT - IDENTIFICATION OF THE DOMAIN ON LAMIN-A REQUIRED FOR ITS INTERACTION

  T OZAKI, M SAIJO, K MURAKAMI, H ENOMOTO, Y TAYA, S SAKIYAMA

  Sep. 1994, ONCOGENE, 9(9) (9), 2649 - 2653, English

  [Refereed]

  Scientific journal


• DEVELOPMENT OF CYCLOPHOSPHAMIDE RESISTANCE IN HUMAN NEUROBLASTOMA XENOGRAFTS

  Tanabe M., Ohnuma N., Enomoto H., Iwai J., Yoshida H., Takahashi H.

  Most patients with neuroblastoma (NB) achieve some response to aggressive chemotherapy. However, some of them have relapse and the tumors subsequently become refractory to drugs. The development of resistance to chemotherapy is a major problem in the treament of NB. We have examined the development of resitance to a high dose of Cyclophosphamide (CPM) in human NB growing as a xenograft (HNX) in nude mice. Three types of HNX (CH-NBI, CH-N-1, CH-NB-4) were treated in consecutive passages with a single dose of 250mg/kg CPM. At each passage the first treated tumor to regrow was transplanted into 10 fresh mice. Of these mice half were treated and half served as controls. This procedure was repeated six times. Growth curves were plotted and the time taken for treated and control groups to double in volume was obtained. Tumor growth delay (TGD) was calculated as the difference between these values. Various changes in TGD produced by repeated CPM treatments were observed in three HNX. TGD dropped from 10.7 to 7.1 days in CH-NB-4 (p < 0.05) at the 2nd transplant and from 9.6 to 7.5 days in CH-N-1 at the 5th transplant and no further decrease was observed by additional treatment in any tumor. TGD was 5.3 days in CH-NB-I at the 1st transplant and no decrease was observed by additional treatment. Treatment with CPM resulted in a rapid reduction in responsiveness to CPM in two HNX but no reduction was observed in one HNX which was considered to have primary resistance to CPM.

  The Japanese Society of Pediatric Surgeons, 1994, Journal of the Japanese Society of Pediatric Surgeons, 30(7) (7), 1261 - 1266, Japanese


• MOLECULAR-CLONING AND CHARACTERIZATION OF A CDNA SHOWING TUMOR-SUPPRESSIVE ACTIVITY IN V-SRC-TRANSFORMED 3Y1 RAT FIBROBLASTS

  S SAKIYAMA, T OZAKI, H ENOMOTO

  1994, ADVANCES IN ENZYME REGULATION, VOL 34, 34, 247 - 255, English

  [Refereed]

  Scientific journal


• PARATESTICULAR NEUROBLASTOMA WITH N-MYC ACTIVATION

  T MATSUNAGA, H TAKAHASHI, N OHNUMA, M TANABE, H YOSHIDA, H ENOMOTO, H HORIE, H SHIRASAWA, B SIMIZU

  Dec. 1993, JOURNAL OF PEDIATRIC SURGERY, 28(12) (12), 1612 - 1614, English

  [Refereed]

  Scientific journal

• Development of the intrinsic and extrinsic innervation of the gut

  Toshihiro Uesaka, Heather M. Young, Vassilis Pachnis, Hideki Enomoto

  Sep. 2016, DEVELOPMENTAL BIOLOGY, 417(2) (2), 158 - 167, English

  [Refereed][Invited]

  Introduction scientific journal


• Retrograde transport of neurotrophic factor signaling: implications in neuronal development and pathogenesis

  Keisuke Ito, Hideki Enomoto

  Aug. 2016, JOURNAL OF BIOCHEMISTRY, 160(2) (2), 77 - 85, English

  [Refereed]

  Book review


• Glial cell line-derived neurotrophic factor is a key regulator for the migration of enteric neural crest derivatives

  Toshihiro Uesaka, Hideki Enomoto

  2011, NEUROSCIENCE RESEARCH, 71, E66 - E67, English

  Summary international conference


• Death comes early: apoptosis observed in ENS precursors

  H. Enomoto

  Jul. 2009, NEUROGASTROENTEROLOGY AND MOTILITY, 21(7) (7), 684 - 687, English

  [Refereed]

  Introduction scientific journal


• Neurotrophic Modulation of Motor Neuron Development

  Thomas W. Gould, Hideki Enomoto

  Feb. 2009, NEUROSCIENTIST, 15(1) (1), 105 - 116, English

  [Refereed]

  Introduction scientific journal


• Genetic model system studies of the development of the enteric nervous system, gut motility and Hirschsprung's disease

  G. Burzynski, I. T. Shepherd, H. Enomoto

  Feb. 2009, NEUROGASTROENTEROLOGY AND MOTILITY, 21(2) (2), 113 - 127, English

  [Refereed]

  Book review


• Mode of gut colonization by enteric neural crest-derived cells

  Hideki Enomoto, Chihiro Nishiyama, Takayuki Manabe, Heather Young, Don Newgreen

  2009, NEUROSCIENCE RESEARCH, 65, S67 - S67, English

  Summary international conference


• Introducing neurocristopathy-associated PHOX2B mutations in mouse reveals conserved pathogenic effects of mutant PHOX2B on mammalian neural crest cell development

  Mayumi Nagashimada, Hideki Enomoto

  2009, NEUROSCIENCE RESEARCH, 65, S157 - S157, English

  Summary international conference


• Bcl-xL-mediated rescue of aganglionosis in a mouse model for Hirschsprung disease

  Toshihiro Uesaka, Hideki Enomoto

  2009, NEUROSCIENCE RESEARCH, 65, S66 - S67, English

  Summary international conference


• Multiple roles of GDNF signaling in development of the enteric nervous system

  Toshihiro Uesaka, Hideki Enomoto

  2008, NEUROSCIENCE RESEARCH, 61, S40 - S40, English

  Summary international conference


• Pleiotropic effects of GDNF in regulation of enteric nervous system development

  Hideki Enomoto

  2006, NEUROSCIENCE RESEARCH, 55, S12 - S12, English

  Summary international conference


• Regulation of neural development by glial cell line-derived neurotrophic factor family ligands

  Hideki Enomoto

  Mar. 2005, Anatomical Science International, 80(1) (1), 42 - 52, English

  [Refereed]

  Introduction scientific journal


• The GDNF family ligands and receptors - implications for neural development

  RH Baloh, H Enomoto, EM Johnson, J Milbrandt

  Feb. 2000, CURRENT OPINION IN NEUROBIOLOGY, 10(1) (1), 103 - 110, English

  [Refereed]

  Book review


• 学生からみた小児外科における臨床実習.

  田辺 政裕, 大沼 直躬, 岩井 潤, 吉田 英生, 榎本 秀樹, 黒田 浩明, 小林 裕之, 岡田 忠明, 高橋 英世

  1997, 医学教育, 28(4) (4), 239 - 243

• Development of the nervous system Physiology of the gastrointestinal tract, Fifth Edition Section II Neurogastroenterology

  Heather M Young, Donald F Newgreen, ENOMOTO HIDEKI

  Joint work, ACADEMIC PRESS, 2012, English

  Scholarly book

• 遺伝性神経芽腫に同定された変異型Phox2Bの機能解析

  原田 俊介, 永島田 まゆみ, 岩﨑 光泰, Enomoto Hideki

  2017年度世界をリードする次世代MD研究者・育成プロジェクト全国リトリート, Dec. 2017, Japanese, *, 神戸, Domestic conference

  Poster presentation


• Pathogenetic Mechanism of Hirschsrung Disease: What Does Mouse Genetics Teach Us?

  Enomoto Hideki

  The 2017 Annual Meeting of Indonesian Society of Human Genetics, Oct. 2017, English, Indonesian Society of Human Genetics, Yogyakarta, Indnesia, International conference

  [Invited]

  Invited oral presentation


• Glial cell-based development and function of the enteric nervous system

  Enomoto Hideki, Uesaka Toshihiro

  第70回日本自律神経学会総会, Aug. 2017, English, 日本自律神経学会, 名古屋, International conference

  Oral presentation


• Enteric neurogenesis from Schwann cell lineage in models of Hirschsprung disease

  Uesaka Toshihiro, Enomoto Hideki

  第40回日本神経科学大会, Jul. 2017, English, 日本神経科学学会, 千葉, Domestic conference

  Oral presentation


• CXCL1抗体は/Xpa/欠損マウスにおけるUVB誘導の皮膚の炎症反応および皮膚腫瘍発生を抑制する

  Kunisada Makoto, 保坂 千恵子, 竹森 千尋, Nakano Eiji, Enomoto Hideki, Nishigori Chikako

  第39回日本光医学・光生物学会, Jul. 2017, Japanese, 日本光医学・光生物学会, 名古屋, Domestic conference

  Oral presentation


• 腸管神経系の発生と病理

  Enomoto Hideki

  慶応義塾大学医学部セミナー, May 2017, Japanese, 慶応医学会例会, 東京, Domestic conference

  [Invited]

  Invited oral presentation


• Plasticity in Schwann cell precursor-derived neurogenesis

  Enomoto Hideki

  50th Annual Meeting of the Japanese Society of Developmental Biologists, May 2017, English, 日本発生生物学会, 東京, Domestic conference

  Oral presentation


• 腸管神経細胞の新たな細胞起源、シュワン細胞前駆細胞

  Enomoto Hideki

  日本解剖学会総会, Mar. 2017, Japanese, 日本解剖学会, 長崎, Domestic conference

  Public symposium


• 腸管神経の発生と病理の分子機構

  Enomoto Hideki

  徳島大学大学院講義, Mar. 2017, Japanese, 徳島大学, 徳島, Domestic conference

  Public discourse


• 腸管神経の発生と病理の分子機構

  Enomoto Hideki

  脳・肝インターフェースメディシン研究センターセミナー, Jan. 2017, Japanese, 脳・肝インターフェースメディシン研究センター, 金沢, Domestic conference

  [Invited]

  Invited oral presentation


• The impact of RET gain-of-function mutation on development of the enteric nervous system

  Enomoto Hideki

  The Australasian Neuroscience Society 36th Annual Scientific Meeting 2016, Dec. 2016, English, The Australasian Neuroscience Society 36th Annual Scientific Meeting 2016, Hobort, Australia, International conference

  [Invited]

  Invited oral presentation


• The effects of Cxcl1 antagonist on UVB-induced skin inflammation in Xeroderma pigmentosum type A deficient mice

  Kunisada Makoto, Chieko Hosaka, Nakano Eiji, Enomoto Hideki, Nishigori Chikako

  16th World Congress on Cancers of the Skin, Aug. 2016, English, Cancers of the Skin, Vienna, オーストリア, International conference

  Poster presentation


• Molecular and Cellular Mechanisms underlying the Development and Pathology of the Enteric Nervous System

  Enomoto Hideki

  Developing Brains,The Nobel Forum, Aug. 2016, English, Karolinska Institute, Stockholm, Sweden, International conference

  [Invited]

  Invited oral presentation


• 腸管神経系の発生と病理における神経前駆細胞の意外な振舞い

  Enomoto Hideki

  第15回生体機能研究会, Jul. 2016, Japanese, 第15回生体機能研究会, 淡路, Domestic conference

  [Invited]

  Invited oral presentation


• Development and pathology of the enteric nervous system

  Enomoto Hideki

  The 5th BRC-MARC Mouse Resource Workshop, Jul. 2016, English, 理化学研究所,南京大学モデル動物実験研究センター, つくば, International conference

  Keynote oral presentation


• 内臓神経系の発生と病理

  Enomoto Hideki

  第22回東北生活習慣病研究会, May 2016, Japanese, 宮城県医師会,田辺三菱製薬株式会社, 仙台, Domestic conference

  [Invited]

  Invited oral presentation


• Enteric neurogenesis from Schwann cell lineage in mouse models of Hirschsprung disease

  Uesaka Toshihiro, Mayumi Nagashimada, Enomoto Hideki

  BMB2015, Dec. 2015, Japanese, 日本分子生物学会The Molecular Biology Society of Japan, 神戸, Domestic conference

  Poster presentation


• Signals regulating migration and differentiation of enteric neural progenitors

  Enomoto Hideki

  University of Melbourne seminar, Nov. 2015, English, University of Melbourne, Melbourne, Australia, International conference

  Public discourse


• Pathogenetic mechanisms underlying the autonomic neurocristopathies

  Enomoto Hideki

  Padiatric Brain Tumor Research Meeting, Nov. 2015, English, Taipei Medical Unversity Hospital, 台北, 台湾, International conference

  Public discourse


• Pathogenetic mechanisms underlying the autonomic neurocristopathies

  Enomoto Hideki

  2015Asia-Pacific Symposium of Neuroblastoma, Nov. 2015, English, Taiwan Neuroblastoma Study Group,Japan Neuroblastoma Study Group,Center of Biotechnology National Taiwan University,Research Center for Developmental and Regenerative Medicine National Taiwan University, 台北, 台湾, International conference

  Keynote oral presentation


• 腸管神経系における神経形成の可塑性

  Enomoto Hideki

  第5回オルソオルガノジェネシス検討会, Aug. 2015, Japanese, オルソオルガノジェネシス検討会, 安曇野, Domestic conference

  Oral presentation


• Cellular origin and behavior of enteric neural progenitors

  Enomoto Hideki

  Inauguration de I' Institut de Biologie seminar, Aug. 2015, English, Inauguration de I' Institut de Biologie, Paris, France, International conference

  Public discourse


• 腸管神経系の発生と発生異常における神経堤細胞の意外な振る舞い

  Enomoto Hideki

  第29回モロシヌス研究会, Jul. 2015, Japanese, モロシヌス研究会, 神戸, Domestic conference

  Keynote oral presentation


• Polarized intracellular trafficking of RET tyrosine kinase in living neurons

  Ito Keisuke, Enomoto Hideki

  The 38th Annual Meeting of the Japan Neuroscience Society, Jul. 2015, English, 日本神経科学, 神戸, Domestic conference

  Poster presentation


• Physiological role of DSCAM in the development of the enteric nervous system

  Iwasaki Mitsuhiro, Enomoto Hideki, Yamakawa Kazuhiro, Amano Kenji

  The 38th Annual Meeting of the Japan Neuroscience Society, Jul. 2015, English, 日本神経科学, 神戸, Domestic conference

  Poster presentation


• Neurogenesis from the Schwann cell lineage in development and disease

  Enomoto Hideki

  The 38th Annual Meeting of the Japan Neuroscience Society, Jul. 2015, English, 日本神経科学, 神戸, Domestic conference

  Public symposium


• Neuronal differentiation from the Schwann cell lineage

  Enomoto Hideki

  48th Annual Meeting for the Japanese Society of Developmental Biologists, Jun. 2015, English, Japanese Society of Developmental Biologists, つくば, Domestic conference

  Public symposium


• 細胞間コミュニケーションから考える神経堤症発症機構

  Enomoto Hideki

  第52回日本小児外科学会学術集会, May 2015, Japanese, The Japanese Society of Padiatric Surgeons, 神戸, Domestic conference

  Keynote oral presentation


• シュワン細胞系譜の持つ神経分化能：発生と疾患への関与

  Enomoto Hideki

  The 104th Annual Meeting of the Japanese Society of Pathology, May 2015, Japanese, 日本病理学会, 名古屋, Domestic conference

  [Invited]

  Invited oral presentation


• The impact of RET gain-of-function mutation on development of the enteric nervous system

  Mitsumasa Okamoto, Uesaka Toshihiro, Keisuke Itoh, Enomoto Hideki

  4th International Symposium on "Development of the enteric nervous system:Cells,Singnals,Genes and Therapy", Apr. 2015, English, ENS meeting scientific organizing committee:Robert Hofstra,Alan Burns(local organizer), Rotterdam, The Netherlands, International conference

  Poster presentation


• Polarized trafficking of RET tyrosine kinase in migrating enteric-neural crestderived cells

  Ito Keisuke, Enomoto Hideki

  4th International Symposium on "Development of the enteric nervous system:Cells,Singnals,Genes and Therapy", Apr. 2015, English, ENS meeting scientific organizing committee:Robert Hofstra,Alan Burns(local organizer), Rotterdam, The Netherlands, International conference

  Poster presentation


• Neurogenesis from Schwann cell lineage in mouse models of Hirschsprung disease

  Uesaka Toshihiro, Mayumi Nagashimada, Enomoto Hideki

  4th International Symposium on "Development of the enteric nervous system:Cells,Singnals,Genes and Therapy", Apr. 2015, English, ENS meeting scientific organizing committee:Robert Hofstra,Alan Burns(local organizer), Rotterdam, The Netherlands, International conference

  Poster presentation


• Down syndrome cell adhesion molecule function in developing enteric nervous system

  Mitsuhiro Iwasaki, Kenji Amano, Kazuhiro Yamakawa, Enomoto Hideki

  4th International Symposium on "Development of the enteric nervous system:Cells,Singnals,Genes and Therapy", Apr. 2015, English, ENS meeting scientific organizing committee:Robert Hofstra,Alan Burns(local organizer), Rotterdam, The Netherlands, International conference

  Poster presentation


• Cellular origin of the enteric nervous system

  Enomoto Hideki

  4th International Symposium on "Development of the enteric nervous system:Cells,Singnals,Genes and Therapy", Apr. 2015, English, ENS meeting scientific organizing committee:Robert Hofstra,Alan Burns(local organizer), Rotterdam, The Netherlands, International conference

  [Invited]

  Invited oral presentation


• Cellular origin and behavior of enteric neural progenitors

  Enomoto Hideki

  2015-2016Digestive Disease Reserch Center(VDDRC)retreat, Apr. 2015, English, Digestive Disease esearch center, Nashville, United States of America, International conference

  Keynote oral presentation


• The cellular origins of the enteric nervous system

  Enomoto Hideki

  The 1st Symposium of Neuroscience Network in Kobe, Feb. 2015, English, 神戸大学, 神戸, Domestic conference

  [Invited]

  Nominated symposium


• Polarized trafficking of RET tyrosine kinase in living cells

  Ito Keisuke, Enomoto Hideki

  Neurovascular Wiring 2nd International Symposium 2015, Jan. 2015, English, 新学術領域研究「血管-神経ワイヤリングにおける相互依存性の正立機構」, 京都, Domestic conference

  Poster presentation


• Identification of Schwann cell precursors as a novel cellular origin of the enteric nervous system

  Enomoto Hideki

  Neurovascular Wiring 2nd International Symposium 2015, Jan. 2015, English, 新学術領域研究「血管-神経ワイヤリングにおける相互依存性の正立機構」, 京都, Domestic conference

  [Invited]

  Nominated symposium


• Schwann Cell Precursors Undergo Neuronal Differentiation and Contribute to the Enteric Nervous System

  Enomoto Hideki

  Gordon Research Conference: Molecular & Cellular Neurobiology, Jul. 2014, English, Gordon Research Conferences, Hong Kong, China, International conference

  [Invited]

  Invited oral presentation


• Schwann cell precursor-like cells are a novel neuronal origin of the enteric nervous system

  Uesaka Toshihiro, Enomoto Hideki

  47th Annual Meeting for the Japanese Society of Development Biologists, May 2014, English, Japanese Society of Developmental Biologists, 名古屋, Domestic conference

  Oral presentation


• Enteric neural crest cells utilize vascular tissue as a migratory scaffold and efficiently colonize the colon

  Enomoto Hideki

  International Vascular Biology Meeting, Apr. 2014, English, 新学術領域研究「血管-神経ワイヤリングにおける相互依存性の正立機構」, 京都, Domestic conference

  [Invited]

  Invited oral presentation


• Analysis of Physiological Meanings of Intracellular Trafficking of the Neurotrophic Receptor, RET – Focusing on Development of the Enteric Nervous System

  Ito Keisuke, Enomoto Hideki

  RIKEN Special Postdoctoral Researchers Program & Foreign Postdoctoral Researchers Program, Poster Session of Research Results, Jan. 2014, English, RIKEN, 和光, Wako, Domestic conference

  Poster presentation


• The Cellular origin of the enteric nervous system.

  Enomoto Hideki

  Gordon Research Conferences on Neural Crest & Cranial Placodes, Jul. 2013, English, Easton, USA, nervous system, International conference

  [Invited]

  Invited oral presentation


• Schwann cell precursor-like cells from the mesentery are a cellular source of enteric neurons

  Uesaka Toshihiro, Enomoto Hideki

  Gordon Research Conferences Neural crest, Jul. 2013, English, Gordon Reserch Conference, Easton, USA, neural crest, International conference

  Poster presentation


• Developmental study of neuroblastoma-associated gene mutations

  Enomoto Hideki

  8th Congress of the international Society for Autonomic Neuroscience, Jul. 2013, English, Giessen, Germany, gene mutations, International conference

  [Invited]

  Invited oral presentation


• Schwann cell precursor-like cells from the mesentery are a cellular origin of enteric neurons

  Uesaka Toshihiro, Enomoto Hideki

  Neuro2013, Jun. 2013, Japanese, Japan Neuroscience Society, 京都, Cellular otigin, Domestic conference

  Poster presentation


• The cellular origin of the enteric nervous system

  Enomoto Hideki

  京都大学再生医科学研究所セミナー, Jun. 2013, Japanese, 京都, Domestic conference

  [Invited]

  Invited oral presentation


• Intracellular Trafficking of a GDNF Receptor, RET- Roles in Neural Development? -

  Ito Keisuke, Enomoto Hideki

  Neuro2013, Jun. 2013, English, The Japan Neuroscience Society, The Japanese Society for Neurochemistry, Japanese Neural Network Society, 京都, Domestic conference

  Oral presentation


• Identification of a novel cellular origin of the enteric nervous system

  Enomoto Hideki

  CDB-IGDB-KAIST joint meeting, Feb. 2013, English, CDB,IGDB,KAIST, kobe, Japan, cellular origin, International conference

  [Invited]

  Invited oral presentation

• Elucidation of the physiology and pathology of Schwann cell-derived neural stem cells

  榎本 秀樹

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Kobe University, 01 Apr. 2022 - 31 Mar. 2025


• 腸-脳機能コネクトミクスによる腸内感覚の機能解明と操作

  榎本 秀樹

  科学技術振興機構, 戦略的な研究開発の推進 戦略的創造研究推進事業 CREST, 神戸大学, 2020 - 2025, Principal investigator

  腸内腔の情報(腸内感覚)は意識に上りませんが、生体恒常性の維持に必須のシグナルです。本研究では、腸内感覚がどのような感覚細胞とニューロン群の相互作用により脳に伝達されるかを、解剖・生理学的定量解析を用いて解明します。さらに腸内感覚を起点とする臓器制御の神経回路を明らかにします。最終的には、腸内感覚の人為的抑制・活性化により、その生理的意義を解明し、腸内感覚による臓器制御法の開発を目指します。


• Regenerative capacity of intrinsic stem cells subjected to disease-causing gene mutations

  榎本 秀樹

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Challenging Research (Exploratory), Kobe University, 30 Jul. 2020 - 31 Mar. 2023

  本研究は、先天疾患を誘導する病的幹細胞が原因遺伝子修復により自律的組織形成能を再獲得できるかを検証することを目的とする。疾患としては先天性の腸管神経幹細胞の異常により広範に神経欠損を起こす難治性ヒルシュスプルング病（HSCR）に焦点をあてる。このモデルマウスで一部の神経幹細胞の正常化を行い、修復神経幹細胞により腸管神経系が正常に形成されるかを解明する。 2021年度は、昨年作製した難治性HSCRモデルマウス２系統の解析・検証を進めた。系統１では、loxP配列に挟まれた優性阻害型RETcDNA（Ret S811F)とそれに続くmCherry cDNAから構成される遺伝子カセットをマウスRet遺伝子座に挿入してある。このヘテロマウスは、腸間神経系欠損を呈し、HSCRと同様の病態が起こることを確認した。このマウスとPhox2B-Creマウスを交配し、RET（S811F)cDNAを発生早期の迷走神経堤細胞で除去したところ、腸管神経欠損のフェノタイプが回避されることを確認した。また、Dhh-Creマウスにより、生後の腸管神経形成を担うシュワン細胞でRET（S811F)cDNAを除去したところ、神経欠損部においてmCherry陽性の腸管神経細胞の増加を認めた。いずれも優勢阻害型変異を除去された細胞が欠損を補償することを示唆する結果であり、解析システムの樹立ができた。 系統2では、Sox10-2A-EGFP cDNAをloxPlox22272で挟み、逆向きにSox10遺伝子座に挿入するカセットを作製した。このベクターを用いて、ES細胞においてgene targetingを行い、相同組換えESクローンを得た。しかし、１匹の高寄与率キメラしか得られず、このキメラは不妊であることが分かった。現在、ES細胞の再injectionによりキメラの数を増やすことによりファウンダー樹立を試みている。


• 腸管神経前駆細胞における網状細胞移動の分子機構解明

  榎本 秀樹

  科学研究費補助金／基盤研究(B), Apr. 2017 - Mar. 2020, Principal investigator

  Competitive research funding


• 臓性一次知覚ニューロンの臓器別カタログ化

  榎本 秀樹

  学術研究助成基金助成金／挑戦的研究（萌芽）, Apr. 2017 - Mar. 2019, Principal investigator

  Competitive research funding


• Management of the research group of Neuro-vascular Wiring

  TAKAHASHI Yoshiko, EMOTO Kazuo, MOCHIZUKI Naoki, KUBOTA Yoshiaki, ENOMOTO Hideki, SEKIGUCHI Kiyotoshi, SEHARA Atsuko, OHTA Kunimasa, SAWAMOTO Kazunobu

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area), 01 Apr. 2010 - 31 Mar. 2016

  平成22年度から平成26年度において行われた新学術領域研究「血管－神経ワイヤリングにおける相互依存性の成立機構」では、生体内二大ネットワークである血管と神経の相互作用の理解を目的とした融合研究が行われた。そこで本年度は、これらの成果取りまとめと成果発信を主な目的として、以下のことを行った。 １．成果取りまとめに関して、本領域の総括班のメンバーを中心とした検討会議を開いた。 ２．国内向け成果公開シンポジウム「血管と神経」を、2016年2月22日に京都大学大学院理学研究科セミナーハウスにて開催した。そこでは、総括班（計画班）が本領域の成果を総括するとともに、公募班から選ばれた４名が「血管と神経」研究に関する最新成果を発表した。 ３．５年間にわたる血管分野と神経分野の融合研究の成果について、領域構成員全員がまとめた研究概要とその研究成果論文を、成果報告集(869ページ）として編纂し発行した。この成果報告集は、関連学術コミュニティおよび全国の研究者に広く配信した。


• (AMED)腸管神経系の形成と維持における組織間相互作用

  榎本 秀樹

  国立研究開発法人日本医療研究開発機構, 革新的先端研究開発支援事業, 2016, Principal investigator

  Competitive research funding


• 腸内の神経前駆細胞の移動を支える血管組織

  榎本 秀樹

  科学研究費補助金／新学術領域研究, Jun. 2010 - Mar. 2015, Principal investigator

  Competitive research funding


• （AMED）腸管神経系の形成と維持における組織間相互作用

  榎本 秀樹

  国立研究開発法人日本医療研究開発機構, クレスト, 2015, Principal investigator

  Competitive research funding


• Molecular Mechanisms underlying a novel form of cell death induced by impaired GDNF signaling

  ENOMOTO Hideki

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), The Institute of Physical and Chemical Research, 2009 - 2011

  Investigation of molecular mechanism underlying caspase-independent cell death of enteric neurons triggered by GDNF deprivation(CI DEN) revealed an intrinsic absence of Apaf-1 function in enteric neurons, which appears to account for the lack in morphological hallmark of apoptosis in CIDEN. Genetic manipulation to block CIDEN in vivo did not cause an increased numbers of enteric neurons, suggesting that CIDEN does not occur in the physiological condition. Blocking CIDEN, however, rescued the intestinal aganglionosis in a mouse model for Hirschsprung disease(HSCR, congenital absence of the enteric ganglia), suggesting that CIDEN is central to the pathogenesis of HSCR.


• GDNFによる運動ニューロンサブタイプの発生制御

  榎本 秀樹, THOMAS・W Gould, GOULD Thomas William

  日本学術振興会, 科学研究費助成事業, 特別研究員奨励費, 独立行政法人理化学研究所, 2006 - 2007

  グリア細胞株由来神経栄養因子(GDNF)は脊髄運動ニューロンの培養下において強力な生存因子として働く。GDNFのノックアウトマウスでは運動ニューロンの数が約40%減少することから、GDNFは生理的に運動ニューロンの生存に関わっていることが知られていた。しかし、GDNFが運動ニューロンの特定のサブセットの生存に関わっているのか、あるいは運動ニューロン全般の生存に関与しているのかは明らかでなかった。申請者は、GDNFの受容体であるRetおよびGFRa1の遺伝子座にGFPやtaulacZ遺伝子をレポーターとして挿入し運動ニューロンの投射を可視化したノックアウトマウスや、Ret, GFRal遺伝子機能を生後または運動ニューロンで特異的に破壊した条件付ノックアウトマウスを用い、腰部運動ニューロン発生におけるRet,GFRalの機能を詳細に解析した。RetやGFRalを運動ニューロンで特異的に欠損させたマウスでは、一部の筋群で運動神経投射異常を起こし、それに対応してごく限られた数のα運動ニューロンの消失が起こることを認めた。これに対し、γ運動ニューロンは脊髄腰部のほぼ全てのレベルで大部分消失していた。一方、生後になってRet, GFRalの機能破壊を起こしたマウスではこのようなγ運動ニューロンの消失は認められなかった。これらの結果は、GDNFシグナルの運動ニューロン生存因子としての作用がγ運動ニューロンにほぼ限定されており、その作用時期は発生過程であることを示していた。これらのデータはGDNFの生理機能、運動ニューロン発生、神経栄養因子の作用の特異性の観点から注目すべき結果であり、近く投稿を予定している。