Updated on 2022/11/25

写真b

 
MORITA Hitoshi
 
*Items subject to periodic update by Rikkyo University (The rest are reprinted from information registered on researchmap.)
Affiliation*
College of Science Department of Life Science
Title*
Assistant Professor
Degree
PhD ( SOKENDAI )
Campus Career*
  • 4 2022 - Present 
    College of Science   Department of Life Science   Assistant Professor
 

Research Areas

  • Life Science / Developmental biology

Research History

  • 4 2022 - Present 
    Rikkyo University   College of Science Department of Life Science   Asistant professor

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  • 4 2019 - 3 2022 
    University of Yamanashi   Asistant professor

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  • 10 2016 - 3 2019 
    University of Yamanashi   Assistant professor

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  • 10 2011 - 9 2016 
    Institute of Science and Technology (IST) Austria   Postdoc

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  • 10 2012 - 9 2014 
    Japan Society for the Promotion of Science (JSPS)

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  • 4 2011 - 9 2011 
    National Institute for Basic Biology (NIBB)   Division of Morphogenesis   Postdoc

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Education

  • 4 2006 - 3 2011 
    The Graduate University for Advanced Studies (SOKENDAI)   School of Life Science   Department of Basic Biology

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  • 4 2002 - 3 2006 
    Chiba University   Faculty of Science   Department of Biology

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Papers

  • Studying YAP-Mediated 3D Morphogenesis Using Fish Embryos and Human Spheroids. Peer-reviewed International journal

    Asaoka Y, Morita H, Furumoto H, Heisenberg CP, Furutani-Seiki M

    Methods in molecular biology (Clifton, N.J.)1893   167 - 181   2019

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    Language:English   Publishing type:Research paper (scientific journal)  

    The transcription coactivator, Yes-associated protein (YAP), which is a nuclear effector of the Hippo signaling pathway, has been shown to be a mechano-transducer. By using mutant fish and human 3D spheroids, we have recently demonstrated that YAP is also a mechano-effector. YAP functions in three-dimensional (3D) morphogenesis of organ and global body shape by controlling actomyosin-mediated tissue tension. In this chapter, we present a platform that links the findings in fish embryos with human cells. The protocols for analyzing tissue tension-mediated global body shape/organ morphogenesis in vivo and ex vivo using medaka fish embryos and in vitro using human cell spheroids represent useful tools for unraveling the molecular mechanisms by which YAP functions in regulating global body/organ morphogenesis.

    DOI: 10.1007/978-1-4939-8910-2_14

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  • Spatiotemporal expression of the cocaine- and amphetamine-regulated transcript-like (cart-like) gene during zebrafish embryogenesis. Peer-reviewed International journal

    Kawahara A, Morita H, Yanagi K, Suzuki H, Mori T, Ohga R, Taimatsu K

    Gene expression patterns : GEP30   1 - 6   8 2018

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    Language:English   Publishing type:Research paper (scientific journal)  

    The cocaine- and amphetamine-regulated transcript (CART) genes are involved in the neural regulation of energy homeostasis; however, their developmental expressions and functions are not fully understood in vertebrates. We have identified a novel zebrafish cart-like gene that encodes a protein of 105 amino acids possessing sequence similarity to zebrafish and mammalian CART proteins. RT-PCR analysis revealed that the cart-like transcripts were maternally supplied and gradually decreased during the cleavage, blastula and gastrula stages; then, transcripts subsequently reaccumulated at the segmentation, pharyngula and hatching stages. Based on a whole-mount in situ hybridization analysis using an antisense cart-like RNA probe, we found that the cart-like transcript was predominantly expressed in both the Rohon-Beard neurons and trigeminal ganglia, suggesting the involvement of the cart-like gene in zebrafish neural development.

    DOI: 10.1016/j.gep.2018.08.002

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  • Developmental expression of the slurp-like1/ly2.3/ly97.3 and slurp-like2/ly2.2/ly97.2 genes during zebrafish early embryogenesis. Peer-reviewed International journal

    Kawahara A, Morita H, Yanagi K, Ishizaka T, Taimatsu K, Ohga R

    Gene expression patterns : GEP30   32 - 36   8 2018

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    Language:English   Publishing type:Research paper (scientific journal)  

    Mammalian SLURP1 and SLURP2 belong to the Ly-6/uPAR superfamily and are involved in maintaining the physiological integrity of keratinocytes. However, the developmental expression and functions of other Ly-6/uPAR family genes in vertebrates are still obscure. We have isolated novel Ly-6/uPAR family genes slurp-like1 (ly2.3/ly97.3) and slurp-like2 (ly2.2/ly97.2) in zebrafish. Both the Slurp-like1 and Slurp-like2 proteins contain the typical signal sequence and carboxy-terminal CCXXXXCN (X: an arbitrary amino acid) consensus sequence of the Ly-6/uPAR family but lack a transmembrane domain and a GPI-anchoring signal sequence, suggesting that both proteins may function as secretory proteins. Whole-mount in situ hybridization analysis revealed that slurp-like1 was predominantly expressed in the floor plate of the neural tube and in the hypochord of the notochord at 24 h post-fertilization (hpf) and detected in the liver and intestinal bulb at 72 hpf, while slurp-like2 was expressed in the midbrain and hindbrain at 24 hpf and detected in the liver and pancreas at 72 hpf. Differential expression profiles of the slurp-like1 and slurp-like2 genes suggest the distinct physiological involvement of these genes in zebrafish early embryogenesis.

    DOI: 10.1016/j.gep.2018.08.006

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  • The Physical Basis of Coordinated Tissue Spreading in Zebrafish Gastrulation Peer-reviewed

    Hitoshi Morita, Silvia Grigolon, Martin Bock, S. F. Gabriel Krens, Guillaume Salbreux, Carl-Philipp Heisenberg

    DEVELOPMENTAL CELL40 ( 4 ) 354 - 366   2 2017

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:CELL PRESS  

    Embryo morphogenesis relies on highly coordinated movements of different tissues. However, remarkably little is known about how tissues coordinate their movements to shape the embryo. In zebrafish embryogenesis, coordinated tissue movements first become apparent during "doming," when the blastoderm begins to spread over the yolk sac, a process involving coordinated epithelial surface cell layer expansion and mesenchymal deep cell intercalations. Here, we find that active surface cell expansion represents the key process coordinating tissue movements during doming. By using a combination of theory and experiments, we show that epithelial surface cells not only trigger blastoderm expansion by reducing tissue surface tension, but also drive blastoderm thinning by inducing tissue contraction through radial deep cell intercalations. Thus, coordinated tissue expansion and thinning during doming relies on surface cells simultaneously controlling tissue surface tension and radial tissue contraction.

    DOI: 10.1016/j.devcel.2017.01.010

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  • Exogenous gene integration mediated by genome editing technologies in zebrafish Peer-reviewed

    Hitoshi Morita, Kiyohito Taimatsu, Kanoko Yanagi, Atsuo Kawahara

    BIOENGINEERED8 ( 3 ) 287 - 295   2017

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    Language:English   Publisher:TAYLOR & FRANCIS INC  

    Genome editing technologies, such as transcription activator-like effector nuclease (TALEN) and the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein (Cas) systems, can induce DNA double-strand breaks (DSBs) at the targeted genomic locus, leading to frameshift-mediated gene disruption in the process of DSB repair. Recently, the technology-induced DSBs followed by DSB repairs are applied to integrate exogenous genes into the targeted genomic locus in various model organisms. In addition to a conventional knock-in technology mediated by homology-directed repair (HDR), novel knock-in technologies using refined donor vectors have also been developed with the genome editing technologies based on other DSB repair mechanisms, including non-homologous end joining (NHEJ) and microhomology-mediated end joining (MMEJ). Therefore, the improved knock-in technologies would contribute to freely modify the genome of model organisms.

    DOI: 10.1080/21655979.2017.1300727

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  • YAP is essential for tissue tension to ensure vertebrate 3D body shape Peer-reviewed

    Sean Porazinski, Huijia Wang, Yoichi Asaoka, Martin Behrndt, Tatsuo Miyamoto, Hitoshi Morita, Shoji Hata, Takashi Sasaki, S. F. Gabriel Krens, Yumi Osada, Satoshi Asaka, Akihiro Momoi, Sarah Linton, Joel B. Miesfeld, Brian A. Link, Takeshi Senga, Atahualpa Castillo-Morales, Araxi O. Urrutia, Nobuyoshi Shimizu, Hideaki Nagase, Shinya Matsuura, Stefan Bagby, Hisato Kondoh, Hiroshi Nishina, Carl-Philipp Heisenberg, Makoto Furutani-Seiki

    NATURE521 ( 7551 ) 217 - +   5 2015

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:NATURE PUBLISHING GROUP  

    Vertebrates have a unique 3D body shape in which correct tissue and organ shape and alignment are essential for function. For example, vision requires the lens to be centred in the eye cup which must in turn be correctly positioned in the head(1). Tissue morphogenesis depends on force generation, force transmission through the tissue, and response of tissues and extracellular matrix to force(2,3). Although a century ago D'Arcy Thompson postulated that terrestrial animal body shapes are conditioned by gravity(4), there has been no animal model directly demonstrating how the aforementioned mechano-morphogenetic processes are coordinated to generate a body shape that withstands gravity. Here we report a unique medaka fish (Oryzias latipes) mutant, hirame (hir), which is sensitive to deformation by gravity. hir embryos display a markedly flattened body caused by mutation of YAP, a nuclear executor of Hippo signalling that regulates organ size. We show that actomyosin-mediated tissue tension is reduced in hir embryos, leading to tissue flattening and tissue misalignment, both of which contribute to body flattening. By analysing YAP function in 3D spheroids of human cells, we identify the Rho GTPase activating protein ARHGAP18 as an effector of YAP in controlling tissue tension. Together, these findings reveal a previously unrecognised function of YAP in regulating tissue shape and alignment required for proper 3D body shape. Understanding this morphogenetic function of YAP could facilitate the use of embryonic stem cells to generate complex organs requiring correct alignment of multiple tissues.

    DOI: 10.1038/nature14215

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  • Cortical Contractility Triggers a Stochastic Switch to Fast Amoeboid Cell Motility Peer-reviewed

    Verena Ruprecht, Stefan Wieser, Andrew Callan-Jones, Michael Smutny, Hitoshi Morita, Keisuke Sako, Vanessa Barone, Monika Ritsch-Marte, Michael Sixt, Raphael Voituriez, Carl-Philipp Heisenberg

    CELL160 ( 4 ) 673 - 685   2 2015

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:CELL PRESS  

    3D amoeboid cell migration is central to many developmental and disease-related processes such as cancer metastasis. Here, we identify a unique prototypic amoeboid cell migration mode in early zebrafish embryos, termed stable-bleb migration. Stable-bleb cells display an invariant polarized balloon-like shape with exceptional migration speed and persistence. Progenitor cells can be reversibly transformed into stable-bleb cells irrespective of their primary fate and motile characteristics by increasing myosin II activity through biochemical or mechanical stimuli. Using a combination of theory and experiments, we show that, in stable-bleb cells, cortical contractility fluctuations trigger a stochastic switch into amoeboid motility, and a positive feedback between cortical flows and gradients in contractility maintains stable-bleb cell polarization. We further show that rearward cortical flows drive stable-bleb cell migration in various adhesive and non-adhesive environments, unraveling a highly versatile amoeboid migration phenotype.

    DOI: 10.1016/j.cell.2015.01.008

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  • Molecular and cellular mechanisms of development underlying congenital diseases Peer-reviewed

    Masakazu Hashimoto, Hitoshi Morita, Naoto Ueno

    CONGENITAL ANOMALIES54 ( 1 ) 1 - 7   2 2014

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    Language:English   Publisher:WILEY-BLACKWELL  

    In the last several decades, developmental biology has clarified the molecular mechanisms of embryogenesis and organogenesis. In particular, it has demonstrated that the tool-kit genes essential for regulating developmental processes are not only highly conserved among species, but are also used as systems at various times and places in an organism to control distinct developmental events. Therefore, mutations in many of these tool-kit genes may cause congenital diseases involving morphological abnormalities. This link between genes and abnormal morphological phenotypes underscores the importance of understanding how cells behave and contribute to morphogenesis as a result of gene function. Recent improvements in live imaging and in quantitative analyses of cellular dynamics will advance our understanding of the cellular pathogenesis of congenital diseases associated with aberrant morphologies. In these studies, it is critical to select an appropriate model organism for the particular phenomenon of interest.

    DOI: 10.1111/cga.12039

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  • Transgenic Xenopus laevis for live imaging in cell and developmental biology Peer-reviewed

    Chiyo Takagi, Kazuhiro Sakamaki, Hitoshi Morita, Yusuke Hara, Makoto Suzuki, Noriyuki Kinoshita, Naoto Ueno

    DEVELOPMENT GROWTH & DIFFERENTIATION55 ( 4 ) 422 - 433   5 2013

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    Language:English   Publisher:WILEY-BLACKWELL  

    The stable transgenesis of genes encoding functional or spatially localized proteins, fused to fluorescent proteins such as green fluorescent protein (GFP) or red fluorescent protein (RFP), is an extremely important research tool in cell and developmental biology. Transgenic organisms constructed with fluorescent labels for cell membranes, subcellular organelles, and functional proteins have been used to investigate cell cycles, lineages, shapes, and polarity, in live animals and in cells or tissues derived from these animals. Genes of interest have been integrated and maintained in generations of transgenic animals, which have become a valuable resource for the cell and developmental biology communities. Although the use of Xenopus laevis as a transgenic model organism has been hampered by its relatively long reproduction time (compared to Drosophila melanogaster and Caenorhabditis elegans), its large embryonic cells and the ease of manipulation in early embryos have made it a historically valuable preparation that continues to have tremendous research potential. Here, we report on the Xenopus laevis transgenic lines our lab has generated and discuss their potential use in biological imaging.

    DOI: 10.1111/dgd.12042

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  • Holding On and Letting Go: Cadherin Turnover in Cell Intercalation Peer-reviewed

    Hitoshi Morita, Carl-Philipp Heisenberg

    DEVELOPMENTAL CELL24 ( 6 ) 567 - 569   3 2013

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    Language:English   Publisher:CELL PRESS  

    DOI: 10.1016/j.devcel.2013.03.007

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  • Cell movements of the deep layer of non-neural ectoderm underlie complete neural tube closure in Xenopus Peer-reviewed

    Hitoshi Morita, Hiroko Kajiura-Kobayashi, Chiyo Takagi, Takamasa S. Yamamoto, Shigenori Nonaka, Naoto Ueno

    DEVELOPMENT139 ( 8 ) 1417 - 1426   4 2012

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:COMPANY OF BIOLOGISTS LTD  

    In developing vertebrates, the neural tube forms from a sheet of neural ectoderm by complex cell movements and morphogenesis. Convergent extension movements and the apical constriction along with apical-basal elongation of cells in the neural ectoderm are thought to be essential for the neural tube closure (NTC) process. In addition, it is known that non-neural ectoderm also plays a crucial role in this process, as the neural tube fails to close in the absence of this tissue in chick and axolotl. However, the cellular and molecular mechanisms by which it functions in NTC are as yet unclear. We demonstrate here that the non-neural superficial epithelium moves in the direction of tensile forces applied along the dorsal-ventral axis during NTC. We found that this force is partly attributable to the deep layer of non-neural ectoderm cells, which moved collectively towards the dorsal midline along with the superficial layer. Moreover, inhibition of this movement by deleting integrin. 1 function resulted in incomplete NTC. Furthermore, we demonstrated that other proposed mechanisms, such as oriented cell division, cell rearrangement and cell-shape changes have no or only minor roles in the non-neural movement. This study is the first to demonstrate dorsally oriented deep-cell migration in non-neural ectoderm, and suggests that a global reorganization of embryo tissues is involved in NTC.

    DOI: 10.1242/dev.073239

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  • Molecular mechanisms of cell shape changes that contribute to vertebrate neural tube closure Peer-reviewed

    Makoto Suzuki, Hitoshi Morita, Naoto Ueno

    DEVELOPMENT GROWTH & DIFFERENTIATION54 ( 3 ) 266 - 276   4 2012

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    Language:English   Publisher:WILEY-BLACKWELL  

    During early development of the central nervous system, the neuroepithelial cells undergo dynamic changes in shape, cumulative action of which cause the neural plate to bend mediolaterally to form the neural tube. The apicobasal elongation changes the cuboidal cells into columnar ones, whereas apical constriction minimizes the cell apices, causing them to adopt wedge-like shapes. To achieve the morphological changes required for the formation of a hollow structure, these cellular changes must be controlled in time and space. To date, it is widely accepted that spatial and temporal changes of the cytoskeletal organization are fundamental to epithelial cell shape changes, and that noncetrosomal microtubules assembled along apicobasal axis and actin filaments and non-muscle myosin II at the apical side are central machineries of cell elongation and apical constriction, respectively. Hence, especially in the last decade, intracellular mechanisms regulating these cytoskeletons have been extensively investigated at the molecular level. As a result, several actin-binding proteins, Rho/ROCK pathway, and cellcell adhesion molecules have been proven to be the central regulators of apical constriction, while the regulatory mechanisms of cell elongation remain obscure. In this review, we first describe the distribution and role of cytoskeleton in cell shape changes during neural tube closure, and then summarize the current knowledge about the intracellular proteins that directly modulate the cytoskeletal organization and thus the neural tube closure.

    DOI: 10.1111/j.1440-169X.2012.01346.x

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  • Nectin-2 and N-cadherin interact through extracellular domains and induce apical accumulation of F-actin in apical constriction of Xenopus neural tube morphogenesis Peer-reviewed

    Hitoshi Morita, Sumeda Nandadasa, Takamasa S. Yamamoto, Chie Terasaka-Iioka, Christopher Wylie, Naoto Ueno

    DEVELOPMENT137 ( 8 ) 1315 - 1325   4 2010

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:COMPANY OF BIOLOGISTS LTD  

    Neural tube formation is one of the most dynamic morphogenetic processes of vertebrate development. However, the molecules regulating its initiation are mostly unknown. Here, we demonstrated that nectin-2, an immunoglobulin-like cell adhesion molecule, is involved in the neurulation of Xenopus embryos in cooperation with N-cadherin. First, we found that, at the beginning of neurulation, nectin-2 was strongly expressed in the superficial cells of neuroepithelium. The knockdown of nectin-2 impaired neural fold formation by attenuating F-actin accumulation and apical constriction, a cell-shape change that is required for neural tube folding. Conversely, the overexpression of nectin-2 in non-neural ectoderm induced ectopic apical constrictions with accumulated F-actin. However, experiments with domain-deleted nectin-2 revealed that the intracellular afadin-binding motif, which links nectin-2 and F-actin, was not required for the generation of the ectopic apical constriction. Furthermore, we found that nectin-2 physically interacts with N-cadherin through extracellular domains, and they cooperatively enhanced apical constriction by driving the accumulation of F-actin at the apical cell surface. Interestingly, the accumulation of N-cadherin at the apical surface of neuroepithelium was dependent on the presence of nectin-2, but that of nectin-2 was not affected by depletion of N-cadherin. We propose a novel mechanism of neural tube morphogenesis regulated by the two types of cell adhesion molecules.

    DOI: 10.1242/dev.043190

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Misc.

Professional Memberships

  •  
    JAPANESE SOCIETY OF DEVELOPMENTAL BIOLOGISTS

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Research Projects

  • Analysis of the role of tissue tension in early heart development

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C) 

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    4 2022 - 3 2027

    Grant number:22K06248

    Grant amount:\4030000 ( Direct Cost: \3100000 、 Indirect Cost:\930000 )

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  • ライブイメージングと定量化による心臓前駆細胞の移動制御機構の解析

    日本学術振興会  科学研究費助成事業 若手研究(B) 

    森田 仁

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    4 2017 - 3 2020

    Authorship:Principal investigator  Grant type:Competitive

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