Updated on 2022/05/25

写真a

 
HANASHIMA, Carina
 
Affiliation
Faculty of Education and Integrated Arts and Sciences, School of Education
Job title
Professor
Homepage URL
https://hanashima-lab.wixsite.com/waseda
Profile
早稲田大学大学院理工学研究科修了
Memorial Sloan Kettering Cancer Center 研究員
Skirball Institute of Biomolecular Medicine 研究員
独立行政法人理化学研究所 大脳皮質発生研究チーム チームリーダー
神戸大学大学院理学研究科 客員准教授
早稲田大学 教育・総合科学学術院 先進理工学研究科 准教授

Concurrent Post

  • Faculty of Science and Engineering   Graduate School of Advanced Science and Engineering

Research Institute

  • 2020
    -
    2022

    理工学術院総合研究所   兼任研究員

Degree

  • 早稲田大学   博士 (理学)

Research Experience

  • 2017.04
    -
    Now

    Waseda University   Facuity of Education and Integrated Arts and science   Associate Professor

  • 2014.04
    -
    2018.03

    Kobe University   School of Medicine

  • 2014.11
    -
    2017.03

    RIKEN

  • 2008.10
    -
    2017.03

    Kobe University   Graduate School of Science, Division of Biology

  • 2015.04
    -
    2016.03

    Osaka University   School of Engineering Science Direct Affiliates

  • 2012.04
    -
    2015.03

    Nara Women's University

  • 2007.09
    -
    2014.11

    理化学研究所 発生・再生科学総合研究センター   チームリーダー

  • 2002.10
    -
    2007.08

    ニューヨーク大学 スカーボール研究所   研究員

  • 1999.10
    -
    2002.09

    米国メモリアル・スローンケタリング癌センター   研究員

▼display all

Professional Memberships

  • 　
    　
    　

    日本分子生物学会

  • 　
    　
    　

    日本神経科学学会

 

Research Areas

  • Neuroscience-general   発生生物学、神経科学

  • Neuroscience-general   発生生物学、神経科学

Research Interests

  • 包括脳ネットワーク

Papers

  • Transcription and Beyond: Delineating FOXG1 Function in Cortical Development and Disorders.

    Pei-Shan Hou, Darren Ó hAilín, Tanja Vogel, Carina Hanashima

    Frontiers in cellular neuroscience   14   35 - 35  2020  [Refereed]  [International journal]

    　View Summary

    Forkhead Box G1 (FOXG1) is a member of the Forkhead family of genes with non-redundant roles in brain development, where alteration of this gene's expression significantly affects the formation and function of the mammalian cerebral cortex. FOXG1 haploinsufficiency in humans is associated with prominent differences in brain size and impaired intellectual development noticeable in early childhood, while homozygous mutations are typically fatal. As such, FOXG1 has been implicated in a wide spectrum of congenital brain disorders, including the congenital variant of Rett syndrome, infantile spasms, microcephaly, autism spectrum disorder (ASD) and schizophrenia. Recent technological advances have yielded greater insight into phenotypic variations observed in FOXG1 syndrome, molecular mechanisms underlying pathogenesis of the disease, and multifaceted roles of FOXG1 expression. In this review, we explore the emerging mechanisms of FOXG1 in a range of transcriptional to posttranscriptional events in order to evolve our current view of how a single transcription factor governs the assembly of an elaborate cortical circuit responsible for higher cognitive functions and neurological disorders.

    DOI PubMed

  • RECK in Neural Precursor Cells Plays a Critical Role in Mouse Forebrain Angiogenesis.

    Huiping Li, Takao Miki, Glícia Maria de Almeida, Carina Hanashima, Tomoko Matsuzaki, Calvin J Kuo, Naoki Watanabe, Makoto Noda

    iScience   19   559 - 571  2019.09  [Refereed]  [International journal]

    　View Summary

    RECK in neural precursor cells (NPCs) was previously found to support Notch-dependent neurogenesis in mice. On the other hand, recent studies implicate RECK in endothelial cells (ECs) in WNT7-triggered canonical WNT signaling essential for brain angiogenesis. Here we report that RECK in NPCs is also critical for brain angiogenesis. When Reck is inactivated in Foxg1-positive NPCs, mice die shortly after birth with hemorrhage in the forebrain, with angiogenic sprouts stalling at the periphery and forming abnormal aggregates reminiscent of those in EC-selective Reck knockout mice and Wnt7a/b-deficient mice. The hemorrhage can be pharmacologically suppressed by lithium chloride. An effect of RECK in WNT7-producing cells to enhance canonical WNT-signaling in reporter cells is detectable in mixed culture but not with conditioned medium. Our findings suggest that NPC-expressed RECK has a non-cell-autonomous function to promote forebrain angiogenesis through contact-dependent enhancement of WNT signaling in ECs, implying possible involvement of RECK in neurovascular coupling.

    DOI PubMed

  • Sensory cortex wiring requires preselection of short- and long-range projection neurons through an Egr-Foxg1-COUP-TFI network.

    Pei-Shan Hou, Goichi Miyoshi, Carina Hanashima

    Nature communications   10 ( 1 ) 3581 - 3581  2019.08  [Refereed]  [International journal]

    　View Summary

    The bimodal requisite for a genetic program and external stimuli is a key feature of sensory circuit formation. However, the contribution of cell-intrinsic codes to directing sensory-specific circuits remains unknown. Here, we identify the earliest molecular program that preselects projection neuron types in the sensory neocortex. Mechanistically, Foxg1 binds to an H3K4me1-enriched enhancer site to repress COUP-TFI, where ectopic acquisition of Foxg1 in layer 4 cells transforms local projection neurons to callosal projection neurons with pyramidal morphologies. Removal of Foxg1 in long-range projection neurons, in turn, derepresses COUP-TFI and activates a layer 4 neuron-specific program. The earliest segregation of projection subtypes is achieved through repression of Foxg1 in layer 4 precursors by early growth response genes, the major targets of the transforming growth factor-β signaling pathway. These findings describe the earliest cortex-intrinsic program that restricts neuronal connectivity in sensory circuits, a fundamental step towards the acquisition of mammalian perceptual behavior.

    DOI PubMed

  • Diencephalic progenitors contribute to the posterior septum through rostral migration along the hippocampal axonal pathway.

    Keisuke Watanabe, Koichiro Irie, Carina Hanashima, Hirohide Takebayashi, Noboru Sato

    Scientific reports   8 ( 1 ) 11728 - 11728  2018.08  [Refereed]  [International journal]

    　View Summary

    Septal nuclei are telencephalic structures associated with a variety of brain functions as part of the limbic system. The two posterior septal nuclei, the triangular septal nucleus (TS) and the bed nuclei of the anterior commissure (BAC), are involved in fear and anxiety through their projections to the medial habenular nucleus. However, the development of both the TS and BAC remains unclear. Here, we found a novel caudal origin and putative migratory stream of mouse posterior septal neurons arising from the thalamic eminence (TE), a transient developmental structure at the rostral end of the rodent diencephalon. TE-derived cells, which have glutamatergic identity, migrated rostrally and entered the telencephalic territory by passing beneath the third ventricle. Subsequently, they turned dorsally toward the posterior septum. We also observed that TS and BAC neurons in the postnatal septum were labeled with GFP by in utero electroporation into the TE, suggesting a shared origin. Furthermore, TE-derived septal neurons migrated along the fornix, an efferent pathway from the hippocampus. These results demonstrate that posterior septal neurons have a distinct extratelencephalic origin from other septal nuclei. This heterogeneous origin may contribute to neuronal diversity of the septal nuclear complex.

    DOI PubMed

  • Evolutionary conservation and conversion of Foxg1 function in brain development.

    Takuma Kumamoto, Carina Hanashima

    Development, growth & differentiation   59 ( 4 ) 258 - 269  2017.05  [Refereed]  [Domestic journal]

    　View Summary

    Among the forkhead box protein family, Foxg1 is a unique transcription factor that plays pleiotropic and non-redundant roles in vertebrate brain development. The emergence of the telencephalon at the rostral end of the neural tube and its subsequent expansion that is mediated by Foxg1 was a key reason for the vertebrate brain to acquire higher order information processing, where Foxg1 is repetitively used in the sequential events of telencephalic development to control multi-steps of brain circuit formation ranging from cell cycle control to neuronal differentiation in a clade- and species-specific manner. The objective of this review is to discuss how the evolutionary changes in cis- and trans-regulatory network that is mediated by a single transcription factor has contributed to determining the fundamental vertebrate brain structure and its divergent roles in instructing species-specific neuronal circuitry and functional specialization.

    DOI PubMed

  • A Sensitive and Versatile In Situ Hybridization Protocol for Gene Expression Analysis in Developing Amniote Brains.

    Pei-Shan Hou, Takuma Kumamoto, Carina Hanashima

    Methods in molecular biology (Clifton, N.J.)   1650 ( 1650 ) 319 - 334  2017  [Refereed]  [International journal]

    　View Summary

    The detection of specific RNA molecules in embryonic tissues has wide research applications including studying gene expression dynamics in brain development and evolution. Recent advances in sequencing technologies have introduced new animal models to explore the molecular principles underlying the assembly and diversification of brain circuits between different amniote species. Here, we provide a step-by-step protocol for a versatile in situ hybridization method that is immediately applicable to a range of amniote embryos including zebra finch and Madagascar ground gecko, two new model organisms that have rapidly emerged for comparative brain studies over recent years. The sensitive detection of transcripts from low to high abundance expression range using the same platform enables direct comparison of gene of interest among different amniotes, providing high-resolution spatiotemporal information of gene expression to dissect the molecular principles underlying brain evolution.

    DOI PubMed

  • Time in Development. Preface.

    Carina Hanashima, Takashi Nishimura, Harukazu Nakamura, Claudio D Stern

    Development, growth & differentiation   58 ( 1 ) 3 - 5  2016.01  [Refereed]  [Domestic journal]

    DOI PubMed

  • Encoding and decoding time in neural development.

    Kenichi Toma, Tien-Cheng Wang, Carina Hanashima

    Development, growth & differentiation   58 ( 1 ) 59 - 72  2016.01  [Refereed]  [Domestic journal]

    　View Summary

    The development of a multicellular organism involves time-dependent changes in molecular and cellular states; therefore 'time' is an indispensable mathematical parameter of ontogenesis. Regardless of their inextricable relationship, there is a limited number of events for which the output of developmental phenomena primarily uses temporal cues that are generated through multilevel interactions between molecules, cells, and tissues. In this review, we focus on neural stem cells, which serve as a faithful decoder of temporal cues to transmit biological information and generate specific output in the developing nervous system. We further explore the identity of the temporal information that is encoded in neural development, and how this information is decoded into various cellular fate decisions.

    DOI PubMed

  • A transportable, inexpensive electroporator for in utero electroporation.

    Torsten Bullmann, Thomas Arendt, Urs Frey, Carina Hanashima

    Development, growth & differentiation   57 ( 5 ) 369 - 377  2015.06  [Refereed]  [Domestic journal]

    　View Summary

    Electroporation is a useful technique to study gene function during development but its broad application is hampered due to the expensive equipment needed. We describe the construction of a transportable, simple and inexpensive electroporator delivering square pulses with varying length and amplitude. The device was successfully used for in utero electroporation in mouse with a performance comparable to that of commercial products.

    DOI PubMed

  • Switching modes in corticogenesis: mechanisms of neuronal subtype transitions and integration in the cerebral cortex.

    Kenichi Toma, Carina Hanashima

    Frontiers in neuroscience   9   274 - 274  2015  [Refereed]  [International journal]

    　View Summary

    Information processing in the cerebral cortex requires the activation of diverse neurons across layers and columns, which are established through the coordinated production of distinct neuronal subtypes and their placement along the three-dimensional axis. Over recent years, our knowledge of the regulatory mechanisms of the specification and integration of neuronal subtypes in the cerebral cortex has progressed rapidly. In this review, we address how the unique cytoarchitecture of the neocortex is established from a limited number of progenitors featuring neuronal identity transitions during development. We further illuminate the molecular mechanisms of the subtype-specific integration of these neurons into the cerebral cortex along the radial and tangential axis, and we discuss these key features to exemplify how neocortical circuit formation accomplishes economical connectivity while maintaining plasticity and evolvability to adapt to environmental changes.

    DOI PubMed

  • The timing of upper-layer neurogenesis is conferred by sequential derepression and negative feedback from deep-layer neurons.

    Kenichi Toma, Takuma Kumamoto, Carina Hanashima

    The Journal of neuroscience : the official journal of the Society for Neuroscience   34 ( 39 ) 13259 - 76  2014.09  [Refereed]  [International journal]

    　View Summary

    The prevailing view of upper-layer (UL) neurogenesis in the cerebral cortex is that progenitor cells undergo successive rounds of asymmetric cell division that restrict the competence and production of UL neurons later in development. However, the recent discovery of UL fate-committed early progenitors raises an alternative perspective concerning their ontogeny. To investigate the emergence of UL progenitors, we manipulated the timing and extent of cortical neurogenesis in vivo in mice. We demonstrated that UL competence is tightly linked to deep-layer (DL) neurogenesis and that this sequence is determined primarily through derepression of Fezf2 by Foxg1 within a closed transcriptional cascade. We further demonstrated that the sequential acquisition of UL competence requires negative feedback, which is propagated from postmitotic DL neurons. Thus, neocortical progenitors integrate intrinsic and extrinsic cues to generate UL neurons through a system that controls the sequence of DL and UL neurogenesis and to scale the production of intracortical projection neurons based on the availability of their subcortical projection neuron counterparts during cortical development and evolution.

    DOI PubMed

  • Neocortical development and evolution.

    Tadashi Nomura, Carina Hanashima

    Neuroscience research   86   1 - 2  2014.09  [Refereed]  [International journal]

    DOI PubMed

  • Neuronal subtype specification in establishing mammalian neocortical circuits

    Takuma Kumamoto, Carina Hanashima

    NEUROSCIENCE RESEARCH   86   37 - 49  2014.09  [Refereed]

    　View Summary

    The functional integrity of the neocortical circuit relies on the precise production of diverse neuron populations and their assembly during development. In recent years, extensive progress has been made in the understanding of the mechanisms that control differentiation of each neuronal type within the neocortex. In this review, we address how the elaborate neocortical cytoarchitecture is established from a simple neuroepithelium based on recent studies examining the spatiotemporal mechanisms of neuronal subtype specification. We further discuss the critical events that underlie the conversion of the stem amniotes cerebrum to a mammalian-type neocortex, and extend these key findings in the light of mammalian evolution to understand how the neocortex in humans evolved from common ancestral mammals. (C) 2014 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

    DOI

  • Robo1 modulates proliferation and neurogenesis in the developing neocortex.

    Mason L Yeh, Yuko Gonda, Mathilda T M Mommersteeg, Melissa Barber, Athena R Ypsilanti, Carina Hanashima, John G Parnavelas, William D Andrews

    The Journal of neuroscience : the official journal of the Society for Neuroscience   34 ( 16 ) 5717 - 31  2014.04  [Refereed]  [International journal]

    　View Summary

    The elaborate cytoarchitecture of the mammalian neocortex requires the timely production of its constituent pyramidal neurons and interneurons and their disposition in appropriate layers. Numerous chemotropic factors present in the forebrain throughout cortical development play important roles in the orchestration of these events. The Roundabout (Robo) family of receptors and their ligands, the Slit proteins, are expressed in the developing forebrain, and are known to play important roles in the generation and migration of cortical interneurons. However, few studies have investigated their function(s) in the development of pyramidal cells. Here, we observed expression of Robo1 and Slit genes (Slit1, Slit2) in cells lining the telencephalic ventricles, and found significant increases in progenitor cells (basal and apical) at embryonic day (E)12.5 and E14.5 in the developing cortex of Robo1(-/-), Slit1(-/-), and Slit1(-/-)/Slit2(-/-), but not in mice lacking the other Robo or Slit genes. Using layer-specific markers, we found that both early- and late-born pyramidal neuron populations were significantly increased in the cortices of Robo1(-/-) mice at the end of corticogenesis (E18.5). The excess number of cortical pyramidal neurons generated prenatally appears to die in early postnatal life. The observed increase in pyramidal neurons was due to prolonged proliferative activity of their progenitors and not due to changes in cell cycle events. This finding, confirmed by in utero electroporation with Robo1 short hairpin RNA (shRNA) or control constructs into progenitors along the ventricular zone as well as in dissociated cortical cell cultures, points to a novel role for Robo1 in regulating the proliferation and generation of pyramidal neurons.

    DOI PubMed

  • 大脳皮質ニューロンの運命決定機構 –時空間制御によるニューロン産生のメカニズム– 「神経幹細胞研究の最前線」

    花嶋かりな

    医学のあゆみ   251   1123 - 1128  2014

  • Robo1 regulates the migration and laminar distribution of upper-layer pyramidal neurons of the cerebral cortex.

    Yuko Gonda, William D Andrews, Hidenori Tabata, Takashi Namba, John G Parnavelas, Kazunori Nakajima, Shinichi Kohsaka, Carina Hanashima, Shigeo Uchino

    Cerebral cortex (New York, N.Y. : 1991)   23 ( 6 ) 1495 - 508  2013.06  [Refereed]  [International journal]

    　View Summary

    Laminar organization is a key feature of the mammalian cerebral cortex, but the mechanisms by which final positioning and "inside-out" distribution of neurons are determined remain largely unknown. Here, we demonstrate that Robo1, a member of the family of Roundabout receptors, regulates the correct positioning of layers II/III pyramidal neurons in the neocortex. Specifically, we used RNA interference in mice to suppress the expression of Robo1 in a subset of layers II/III neurons, and observed the positions of these cells at distinct developmental stages. In contrast to control neurons that migrated toward the pial surface by P1, Robo1-suppressed neurons exhibited a delay in entering the cortical plate at respective stages. Unexpectedly, after the first postnatal week, these neurons were predominantly located in the upper part of layers II/III, in contrast to control cells that were distributed throughout these layers. Sequential electroporation studies revealed that Robo1-suppressed cells failed to establish the characteristic inside-out neuronal distribution and, instead, they accumulated beneath the marginal zone regardless of their birthdate. These results demonstrate that Robo receptors play a crucial role in neocortical lamination and particularly in the positioning of layers II/III pyramidal neurons.

    DOI PubMed

  • Foxg1 coordinates the switch from nonradially to radially migrating glutamatergic subtypes in the neocortex through spatiotemporal repression.

    Takuma Kumamoto, Ken-ichi Toma, Gunadi, William L McKenna, Takeya Kasukawa, Sol Katzman, Bin Chen, Carina Hanashima

    Cell reports   3 ( 3 ) 931 - 45  2013.03  [Refereed]  [International journal]

    　View Summary

    The specification of neuronal subtypes in the cerebral cortex proceeds in a temporal manner; however, the regulation of the transitions between the sequentially generated subtypes is poorly understood. Here, we report that the forkhead box transcription factor Foxg1 coordinates the production of neocortical projection neurons through the global repression of a default gene program. The delayed activation of Foxg1 was necessary and sufficient to induce deep-layer neurogenesis, followed by a sequential wave of upper-layer neurogenesis. A genome-wide analysis revealed that Foxg1 binds to mammalian-specific noncoding sequences to repress over 12 transcription factors expressed in early progenitors, including Ebf2/3, Dmrt3, Dmrta1, and Eya2. These findings reveal an unexpected prolonged competence of progenitors to initiate corticogenesis at a progressed stage during development and identify Foxg1 as a critical initiator of neocorticogenesis through spatiotemporal repression, a system that balances the production of nonradially and radially migrating glutamatergic subtypes during mammalian cortical expansion.

    DOI PubMed

  • Quantitative expression profile of distinct functional regions in the adult mouse brain.

    Takeya Kasukawa, Koh-hei Masumoto, Itoshi Nikaido, Mamoru Nagano, Kenichiro D Uno, Kaori Tsujino, Carina Hanashima, Yasufumi Shigeyoshi, Hiroki R Ueda

    PloS one   6 ( 8 ) e23228  2011  [Refereed]  [International journal]

    　View Summary

    The adult mammalian brain is composed of distinct regions with specialized roles including regulation of circadian clocks, feeding, sleep/awake, and seasonal rhythms. To find quantitative differences of expression among such various brain regions, we conducted the BrainStars (B*) project, in which we profiled the genome-wide expression of ∼50 small brain regions, including sensory centers, and centers for motion, time, memory, fear, and feeding. To avoid confounds from temporal differences in gene expression, we sampled each region every 4 hours for 24 hours, and pooled the samples for DNA-microarray assays. Therefore, we focused on spatial differences in gene expression. We used informatics to identify candidate genes with expression changes showing high or low expression in specific regions. We also identified candidate genes with stable expression across brain regions that can be used as new internal control genes, and ligand-receptor interactions of neurohormones and neurotransmitters. Through these analyses, we found 8,159 multi-state genes, 2,212 regional marker gene candidates for 44 small brain regions, 915 internal control gene candidates, and 23,864 inferred ligand-receptor interactions. We also found that these sets include well-known genes as well as novel candidate genes that might be related to specific functions in brain regions. We used our findings to develop an integrated database (http://brainstars.org/) for exploring genome-wide expression in the adult mouse brain, and have made this database openly accessible. These new resources will help accelerate the functional analysis of the mammalian brain and the elucidation of its regulatory network systems.

    DOI PubMed

  • 大脳皮質グルタミン酸作動性細胞の特異性を決定する分子の探索(A screen for molecules that determine the specification of cortical upper-layer glutamatergic neurons)

    権田 裕子, 水谷 健一, 當麻 憲一, 花嶋 かりな

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集   83回・33回   1P - 0736  2010.12

  • 発生期大脳皮質における神経前駆細胞の経時的遺伝子発現解析(Molecular Identity of Temporal Neuronal Precursors in the Mouse Neocortex)

    當麻 憲一, 水谷 健一, 権田 裕子, 花嶋 かりな

    神経化学   49 ( 2-3 ) 621 - 621  2010.08

  • Pyramidal neurons grow up and change their mind

    Gord Fishell, Carina Hanashima

    NEURON   57 ( 3 ) 333 - 338  2008.02  [Refereed]

    　View Summary

    The precise stereotypic projections of pyramidal neurons within the six-layered cortex of mammals are key in allowing this structure to attain its high level of function. Recent studies have provided the first indications that postmitotic transcription factors are required for the formation and maintenance of both corticofugal and intracortical pyramidal cell populations. Here, we discuss these new findings in the context of our present understanding of cortical cell specification.

    DOI PubMed

  • The role of Foxg1 and dorsal midline signaling in the generation of Cajal-Retzius subtypes.

    Carina Hanashima, Marie Fernandes, Jean M Hebert, Gord Fishell

    The Journal of neuroscience : the official journal of the Society for Neuroscience   27 ( 41 ) 11103 - 11  2007.10  [Refereed]  [International journal]

    　View Summary

    Cajal-Retzius (CR) cells, the earliest-born neurons in the neocortex, arise from discrete sources within the telencephalon, including the dorsal midline and the pallial-subpallial boundary (PSB). In particular, the cortical hem, a region of high bone morphogenetic proteins (BMPs) and Wnt (wingless-type MMTV integration site family) expression but lacking in Foxg1 (forkhead box G1) is a major source of CR neurons. Whether CR cells from distinct origins arise from disparate developmental processes or share a common mechanism is unclear. To elucidate the molecular basis of CR cell development, we assessed the role of both Foxg1 and dorsal midline signaling in the production of cortical hem- and PSB-derived CR cells. We demonstrate that the loss of Foxg1 results in the overproduction of both of these CR populations. However, removal of Foxg1 at embryonic day 13, although expanding the number of CR cells with a PSB phenotype, does not result in an expansion of BMPs or Wnts in the dorsomedial signaling center. Conversely, loss of the dorsal midline ligands as observed in Gli3 (glioma-associated oncogene homolog 3) mutants results in the loss of the cortical hem-derived CR character but does not affect the specification of PSB-derived CR cells. Hence, our findings demonstrate that, although the specification of cortical hem-derived CR cells is dependent on signaling from the dorsal midline, Foxg1 functions to repress the generation of both cortical hem- and PSB-derived CR cells.

    DOI PubMed

  • Building bridges to the cortex.

    Carina Hanashima, Zoltán Molnár, Gord Fishell

    Cell   125 ( 1 ) 24 - 7  2006.04  [Refereed]  [International journal]

    　View Summary

    Innervation of the neocortex by the thalamus is dependent on the precise coordination of spatial and temporal guidance cues. In this issue of Cell, work by López-Bendito et al.(2006) reveals that tangentially migrating cells within the ventral telencephalon are essential for axonal navigation between the thalamus and the neocortex, a process apparently mediated by Neuregulin-1/ErbB4 short- and long-range signaling.

    DOI PubMed

  • Foxg1 suppresses early cortical cell fate.

    Carina Hanashima, Suzanne C Li, Lijian Shen, Eseng Lai, Gord Fishell

    Science (New York, N.Y.)   303 ( 5654 ) 56 - 9  2004.01  [Refereed]  [International journal]

    　View Summary

    During mammalian cerebral corticogenesis, progenitor cells become progressively restricted in the types of neurons they can produce. The molecular mechanism that determines earlier versus later born neuron fate is unknown. We demonstrate here that the generation of the earliest born neurons, the Cajal-Retzius cells, is suppressed by the telencephalic transcription factor Foxg1. In Foxg1 null mutants, we observed an excess of Cajal-Retzius neuron production in the cortex. By conditionally inactivating Foxg1 in cortical progenitors that normally produce deep-layer cortical neurons, we demonstrate that Foxg1 is constitutively required to suppress Cajal-Retzius cell fate. Hence, the competence to generate the earliest born neurons during later cortical development is actively suppressed but not lost.

    DOI PubMed CiNii

  • Brain factor-1 controls the proliferation and differentiation of neocortical progenitor cells through independent mechanisms.

    Carina Hanashima, Lijian Shen, Suzanne C Li, Eseng Lai

    The Journal of neuroscience : the official journal of the Society for Neuroscience   22 ( 15 ) 6526 - 36  2002.08  [Refereed]  [International journal]

    　View Summary

    The winged helix gene Brain factor-1 (BF1) has a pleiotropic role in the development of the cerebral hemispheres of the brain. Mice lacking BF1 have defects in the morphogenesis of the structures of the dorsal telencephalon (e.g., neocortex) and the ventral telencephalon (e.g., the basal ganglia). This study focuses on the functions of BF1 in the dorsal telencephalon. We showed previously that telencephalic progenitor cells lacking BF1 differentiate into neurons prematurely. Here, we demonstrate that the loss of BF1 also results in an early lengthening of the cell cycle in neocortical progenitors. To investigate the mechanisms by which BF1 regulates progenitor cell proliferation and differentiation in the developing brain, we have replaced the endogenous BF1 protein with a DNA binding defective form of BF1 in mice, BF1(NHAA). The BF1(NHAA) protein restores the growth of the dorsal telencephalon, by improving the proliferation of progenitor cells. However, the BF1(NHAA) protein does not correct the early neuronal differentiation associated with the loss of BF1. In contrast, replacement of endogenous BF1 with wild-type BF1 corrects the defects in both the proliferation and differentiation of neocortical progenitors. These results demonstrate that BF1 controls progenitor cell proliferation and differentiation in the neocortex through distinct DNA binding-independent and binding-dependent mechanisms.

    PubMed

  • Cytotoxic and growth inhibitory effect of ascorbic acid on cultured bovine vascular endothelial cells

    C Hanashima, H Namiki

    ZOOLOGICAL SCIENCE   16 ( 1 ) 99 - 104  1999.02  [Refereed]

    　View Summary

    Ascorbic acid (AsA) is highly concentrated in vitreous in bovine, human as well as in other species. In order to evaluate the role of ascorbic acid as an ocular neovascularization inhibitor, we examined the effect of ascorbic acid on growth and survival of cultured vascular endothelial cells. When added to culture medium, high concentration of ascorbic acid (0.3 mM<) reduced viability of bovine aortic endothelial cells (BAEC) within 24 hr. Morphology of ascorbic acid treated endothelial cells demonstrated that fragmentation of nuclei does not accompany during this incubation period, suggesting that ascorbic acid induces vascular endothelial cell death in a non-apoptotic manner. To further confirm that this event was not specific on BAEC, bovine retinal endothelial cells (BREC) and human aortic endothelial cells (HAEC) were tested for ascorbic acid cytotoxicity. Ascorbic acid induced cell death in all three types of cells, but the dose required for induction of cell death differed, human endothelial cells were apparently more resistant to ascorbic acid cytotoxicity than bovine cells. Decrease in viability of BAEC exposed to ascorbic acid were partially inhibited by exposure to low oxygen concentration (O-2 = 1%). Addition of vascular endothelial growth factor (VEGF) stimulated proliferation of both BAEC and BREC, but cc-addition of ascorbic acid reduced VEGF-induced endothelial cell proliferation. These results show that ascorbic acid modulates endothelial cell behavior in vitro and suggest that it is a negative regulator for ocular neovascularization.

  • Reduced viability of vascular endothelial cells by high concentration of ascorbic acid in vitreous humor

    C Hanashima, H Namiki

    CELL BIOLOGY INTERNATIONAL   23 ( 4 ) 287 - 298  1999  [Refereed]

    　View Summary

    Normal mammalian vitreous humor maintains its avascularity after regression of hyaloid vessels. Neovascularization in adults is only detected under pathological conditions which suggests that antiangiogenic factors are present in the vitreous humor. To elucidate the mechanism of vitreal angiogenic inhibition, we investigated the effect of vitreous humor on cultured vascular endothelial cells. When bovine aortic endothelial cells were cultured in the presence of bovine vitreous humor in medium, a decrease in cell viability was observed within 24 h. Ascorbic acid from vitreous humor has been identified as a cell death inducing factor with high performance liquid chromatography (HPLC) and molecular mass analysis. Ascorbic acid reduced endothelial cell viability at concentrations normally present in vitreous humor. This effect was completely inhibited by antioxidants, N-acetylcysteine and catalase. Amongst the ascorbic acid derivatives tested, ascorbic acid 2-phosphate did not induce cell death, suggesting that the production of ascorbyl radical is required for induction of cell death. Furthermore, capillary formation in three-dimensional collagen gel cultures characteristic of vascular endothelial cells were disrupted in the presence of ascorbic acid. Since ascorbic acid is highly concentrated in ocular tissues, especially in vitreous humor, it may function as a neovascularization inhibitor. (C) 1999 Academic Press.

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Books and Other Publications

  • 大脳皮質ニューロンの運命決定機構 –時空間制御によるニューロン産生のメカニズム–

    花嶋かりな( Part： Sole author)

    医学のあゆみ. 251, 1123-1128.  2014

  • 「ROBO」 脳科学辞典 脳科学辞典編集委員会編.

    花嶋かりな, 権田裕子( Part： Joint author)

    2012

  • Symmetric versus asymmeteric cell division of the cortex.

    Fishell G, Hanashima C( Part： Joint author, 785-791.)

    In Encyclopedia of Neuroscience, L. Squire (Ed.)  2009

  • 大脳皮質ニューロンの運命決定機構.「神経回路の制御と脳機能発現の メカニズム」.

    花嶋かりな( Part： Sole author)

    実験医学・増刊号 137: 1832-1838  2008

Misc

  • Foxg1 coordinates the early transition of temporal cell identity in the cerebral cortex

    Takuma Kumamoto, Ken-ichi Toma, Gunadi, Bin Chen, Carina Hanashima

    INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE   30 ( 8 ) 679 - 679  2012.12

    Research paper, summary (international conference)  

    DOI

  • Foxg1 coordinates the timing of projection neuron production in the cerebral cortex

    Carina Hanashima, Takuma Kumamoto, Ken-ichi Touma

    NEUROSCIENCE RESEARCH   71   E227 - E227  2011

    Research paper, summary (international conference)  

    DOI

  • Molecular mechanisms of upper-layer neuron specification in mouse neocortex

    Ken-ichi Toma, Yuko Gonda, Ken-ichi Mizutani, Carina Hanashima

    NEUROSCIENCE RESEARCH   71   E330 - E330  2011

    Research paper, summary (international conference)  

    DOI

  • Foxg1 regulates the onset of projection neuron production in the neocortex

    Takuma Kumamoto, Gunadi Gunadi, Ken-ichi Mizutani, Carina Hanashima

    NEUROSCIENCE RESEARCH   68   E370 - E370  2010

    Research paper, summary (international conference)  

    DOI

  • Robo1 regulates the morphological development of pyramidal neurons in the mouse neocortex

    Yuko Gonda, Masayuki Sekiguchi, Hidenori Tabata, Takashi Namba, Keiji Wada, Kazunori Nakajima, Carina Hanashima, Shigeo Uchino, Shinichi Kohsaka

    NEUROSCIENCE RESEARCH   68   E63 - E63  2010

    Research paper, summary (international conference)  

    DOI

  • Molecular identity of temporal neuronal precursors in the mouse neocortex

    Ken-ichi Toma, Ken-ichi Mizutani, Yuko Gonda, Carina Hanashima

    NEUROSCIENCE RESEARCH   68   E245 - E245  2010

    Research paper, summary (international conference)  

    DOI

  • Characterization of temporal identity of neuronal progenitor cells in the neocortex

    Ken-ichi Mizutani, Carina Hanashima

    NEUROSCIENCE RESEARCH   65   S157 - S157  2009

    Research paper, summary (international conference)  

    DOI

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Awards

  • Poster Award

    2012.10   Asia-Pacific Developmental Biology Conference APDBC   Foxg1 Coordinates the Switch from Non-Radially to Radially Migrating Glutamatergic Subtypes in the Neocortex through Spatiotemporal Repression.

    Winner： Kumamoto T, Toma K, Gunadi, McKenna W, Chen B, Hanashima C

Research Projects

  • 細胞間情報伝達を介した発生時間制御機構

    科学研究費補助金 新学術領域研究（研究領域提案型）領域名称「脳構築における発生時計と場の連携」(文部科学省） 

    Project Year :

    2016
    -
    2020
     

    花嶋かりな

  • 初期ニューロンを介した大脳新皮質構築機構の解明

    科学研究費補助金 基盤研究B （文部科学省） 

    Project Year :

    2016
    -
    2018
     

    花嶋かりな

  • 順行性ウイルスベクターを用いた近く神経回路形成機構の解析

    科学研究費補助金 挑戦的萌芽研究（文部科学省） 

    Project Year :

    2016
    -
    2017
     

    花嶋かりな

  • 大脳皮質上層ニューロンの分化決定機構の解明

    科学研究費補助金（研究領域提案型）「神経細胞の多様性と大脳皮質の構築」(文部科学省） 

    Project Year :

    2013
    -
    2014
     

    花嶋かりな

  • 大脳皮質神経細胞の運命決定機構の解明

    科学研究費補助金 基盤研究C (文部科学省） 

    Project Year :

    2012
    -
    2014
     

    花嶋かりな

  • 大脳皮質神経細胞 産生プログラムの移行制御機構の解明

    科学研究費補助金(文部科学省）  新学術領域研究（研究領域提案型）「神経細胞の多様性と大脳新皮質の構築」

    Project Year :

    2011
    -
    2012
     

    花嶋かりな

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Presentations

  • Establishing neuronal identity in the cerebral cortex.

    Carina Hanashima  [Invited]

    Volga Neuroscience Meeting 

    Presentation date： 2016.07

  • Mechanisms that establish neuronal identity in the cerebral cortex.

    Carina Hanashima

    3rd International Symposium on ‘Neocortical Organization 

    Presentation date： 2016.02

  • A two-step regulatory mechanism determine the timing of upper-layer neurogenesiss in the cerebral cortex.

    Toma, K, Kumamoto, T, Hanashima, C

    Neuroscience2015 

    Presentation date： 2015.07

  • Integrative mechanisms of layer IV neuron development in the neocortex.

    Wang, T.C, Toma,K, Hanashima, C

    Neuroscience2015第38回日本神経科学大会 

    Presentation date： 2015.07

  • Neuronal fate specification in establishing the neocortex. Symposium on ‘Vertebrate brains: Structure, Function and Evolution’

    Carina Hanashima  [Invited]

    The 48th Annual Meeting of the Japan Society of Developmental Biologists. 

    Presentation date： 2015.06

  • Development and evolutionary origin of the neocortex.

    Kumamoto, T, Hanashima, C

    CDB Symposium 2015, ‘Time in Development’ Symposium 2015 

    Presentation date： 2015.03

  • Robo1 regulates dendritic development of neocortical pyramidal neurons.

    Gonda, Y, Hanashima, C

    CDB Symposium 2015 

    Presentation date： 2015.03

  • A two-step regulatory mechanism determines the timing of upper-layer neurogenesis in the cerebral cortex.

    Toma, K, Kumamoto, T, Hanashima, C

    CDB Symposium 2015, ‘Time in Development’ Symposium 2015 

    Presentation date： 2015.03

  • Temporal Control of Neuronal Identity in the Cerebral Cortex.

    Carina Hanashima

    CDB Symposium 

    Presentation date： 2015.03

  • Molecular mechanisms for dendritogenesis of neocortical pyramidal neurons

    Yuko Gonda, Hanashima.C

    第37回日本分子生物学年会 

    Presentation date： 2014.11

  • Temporal and Spatial Control of Neuronal Identity in the Cerebral Cortex

    Carina Hanashima  [Invited]

    China-Japan-Korea Joint Symposium in Developmental Biology. 

    Presentation date： 2014.10

  • 大脳皮質発生における神経細胞特異的なRNA結合蛋白質Nova1の同定と解析

    Wang, T.C, Toma,K, Hanashima, C

    Neuroscience2014 

    Presentation date： 2014.09

  • 軸索ガイダンス分子を介した大脳皮質神経細胞の形態形成機構

    Yuko, Gonda, Hanashima,C

    Neuroscience2014 

    Presentation date： 2014.09

  • 大脳皮質上層ニューロンの分化決定機構

    Toma, K, Kumamoto, T, Hanashima, C

    Neuroscience2014 

    Presentation date： 2014.09

  • 哺乳類大脳新皮質獲得を可能にした分子メカニズムの解析

    隈元拓馬, 花嶋かりな

    Neuroscience2014: 第37回日本神経科学大会 

    Presentation date： 2014.09

  • Mechanisms that determine the timing of upper-layer neurogenesis in the cerebral cortex.

    Toma, K, Kumamoto, T, Hanashima, C

    Cortical Development 

    Presentation date： 2014.05

  • Laminar-specific control of neuronal distribution and dendritic patterning by axon guidance molecules.

    Gonda, Y, Andrews, W.D, Chedotal, A, Parnavelas, J.G, Hanashima, C  [Invited]

    Cortical Development 

    Presentation date： 2014.05

  • Molecular logic underlying the origin of the neocortex

    Kumamoto, T, Hanashima, C  [Invited]

    Cortical Development 

    Presentation date： 2014.05

  • Neuronal Specification in Establishing Mammalian Neocortical Circuits.

    Carina Hanashima  [Invited]

    2nd International Symposium on ‘Neocortical Organization’ 

    Presentation date： 2013.11

  • Molecular Logic underlying the Origin of the Neocortex.

    Kumamoto, T, Hanashima, C

    Presentation date： 2013.06

  • Neuronal Specification in Establishing Mammalian Neocortical Circuits. Symposium ‘Neocortical Development and Circuit Formation - How is the Mammalian-Specific Brain Structure Formed?’

    Carina Hanashima

    The 36th Annual Meeting of the Japan Neuroscience Society 

    Presentation date： 2013.06

  • Temporal and Spatial Control of Neuronal Identity in the Brain.

    Carina Hanashima  [Invited]

    MRC Centre for Developmental Neurobiology. 

    Presentation date： 2013.01

  • Foxg1による大脳皮質神経細胞分化の時空間的制御.

    隈元拓馬, 花嶋かりな

    第35回 日本分子生物学会年会16. ワークショップ ‘脳神経系の形成過程における神経幹細胞の増殖・分化制御’ 

    Presentation date： 2012.12

  • Foxg1 Coordinates the Switch from Non-Radially to Radially Migrating Glutamatergic Subtypes in the Neocortex through Spatiotemporal Repression.

    Kumamoto T, Toma K, Gunadi, McKenna W, Chen B, Hanashima C

    Asia-Pacific Developmental Biology Conference APDBC 

    Presentation date： 2012.10

  • Foxg1 directs the specification of upper-layer projection neurons in the late neocortical progenitors. Nanosymposium on ‘ Cell Lineage and Differentiation

    Toma K, Hanashima, C

    Neuroscience 2012 SfN 42nd Annual Meeting 

    Presentation date： 2012.10

  • Regulation of Neuronal Subtype Identity Transition in the Cerebral Cortex.

    Carina Hanashima  [Invited]

    The 35th Annual Meeting of the Japan Neuroscience Society 

    Presentation date： 2012.09

  • “ Temporal requirement for Robo1 in the development of neocortical pyramidal neurons ”

    Gonda Y, Andrews W, Parnavelas J, Hanashima C

    第35回日本神経科学大会 

    Presentation date： 2012.09

  • 新規カハール・レチウス細胞マーカー遺伝子の探索と発現解析

    隈元拓馬, 花嶋かりな

    包括脳夏のワークショップ 

    Presentation date： 2012.07

  • “ A conditional gene expression system to study layer-specific dendrite development of neocortical pyramidal neurons”

    Gonda, Y, Hanashima, C  [Invited]

    包括脳夏のワークショップ 

    Presentation date： 2012.07

  • Foxg1 is required in late mouse neocortical progenitors to direct differentiation of upper-layer projection neurons.

    Toma K, Takuma Kumamoto, Hanashima C

    ISSCR2012, The ISSCR 10th Annual Meeting, 

    Presentation date： 2012.06

  • Roles of subplate neurons in establishing neocortical regional identity. Foxg1 regulates the onset of projection neuron production in the neocortex.

    Bullmann T, Hanashima C

    Joint meeting of The 45th Annual Meeting of the Japanese Society of Developmental Biologists & The 64th Annual Meeting of the Japanese Society for Cell Biology 

    Presentation date： 2012.05

  • Spatiotemporal repression coordinates projection neuron production onset in the cerebral cortex.

    Kumamoto T, Toma K, Gunadi, McKenna W, Chen B, Hanashima C

    Joint meeting of The 45th Annual Meeting of the Japanese Society of Developmental Biologists & The 64th Annual Meeting of the Japanese Society for Cell Biology 

    Presentation date： 2012.05

  • The role of Robo1 in the morphological development of cortical upper-layer pyramidal neurons

    Gonda Y, Andrews W, Tabata H, Namba T, Nakajima K, Parnavelas J, Kohsaka S, Uchino S, Hanashima C

    Joint meeting of The 45th Annual Meeting of the Japanese Society of Developmental Biologists & The 64th Annual Meeting of the Japanese Society for Cell Biology 

    Presentation date： 2012.05

  • Molecular Control of Projection Neuron Identity in the Cerebral Cortex.

    Carina Hanashima  [Invited]

    BIT’s 3rdAnnual World Congress of NeuroTalk 

    Presentation date： 2012.05

  • Robo1 controls the migration and laminar distribution of cortical upper-layer pyramidal neurons

    Gonda Y, Andrews W, Tabata H, Namba T, Nakajima K, Parnavelas J, Kohsaka S, Uchino S, Hanashima C

    1st International Symposium “Neocortical Organization 

    Presentation date： 2012.03

  • Foxg1 regulates the onset of projection neuron production in the cerebral cortex.

    Kumamoto T, Toma K, Gunadi, McKenna W, Kasukawa T, Chen B, Hanashima C

    1st International symposium: Neocortical Organization, 

    Presentation date： 2012.03

  • Regulation of Early Identity Transition in the Cerebral Cortex.

    Carina Hanashima

    The 59th NIBB Conference ‘Neocortical Organization 

    Presentation date： 2012.03

  • Foxg1 coordinates the early transition of temporal cell identity in the cerebral cortex.

    Kumamoto T, Toma K, Gunadi, Chen B, Hanashima C

    19th Biennial Meeting of the International Society for Developmental Neuroscience. 

    Presentation date： 2012.01

  • Foxg1 is required for the specification of upper-layer neurons in the neocortex.

    Toma K, Kumamoto T, Hanashima C

    MBSJ2011 

    Presentation date： 2011.12

  • Robo1 controls the laminar distribution and dendritic development of cortical upper-layer neurons

    Gonda Y, Andrews W, Tabata H, Namba T, Nakajima K, Parnavelas J, Kohsaka S, Uchino S, Hanashima C

    Presentation date： 2011.12

  • Robo1 controls the laminar distribution and dendritic development of cortical upper-layer neurons. ‘Development and Regeneration, Neuroscience’

    Gonda,Yuko, Carina Hanashima

    第34回 日本分子生物学会年会 

    Presentation date： 2011.12

  • Robo1 regulates the migration and laminar distribution of upper-layer pyramidal neurons

    Gonda Y, Andrews W, Nakajima K, Parnavelas J, Hanashima C

    Neuroscience2011 

    Presentation date： 2011.11

  • Molecular mechanisms of upper-layer neuron specification in the developing neocortex.

    Toma K, Kumamoto T, Hanashima C

    The exciting biology meeting on “Cellular development: Biology at the interface 

    Presentation date： 2011.09

  • Robo1 regulates the laminar distribution and morphological development of upper-layer pyramidal neurons

    Gonda Y, Andrews W, Nakajima K, Parnavelas J, Hanashima C

    Cellular development: biology at the interface 

    Presentation date： 2011.09

  • Molecular mechanisms of upper-layer neuron specification in mouse neocortex.

    Toma K, Yuko Gonda, Ken-ichi Mizutani, Hanashima C

    Presentation date： 2011.09

  • Foxg1 coordinates the timing of projection neuron production in the cerebral cortex.

    Hanashima C, Kumamoto T, Ken-ichi Toma

    Neuroscience2011, 第34回日本神経科学会年会 

    Presentation date： 2011.09

  • Robo1 controls the laminar distribution and morphological development of upper-layer pyramidal neurons

    Gonda Y, Andrews W, Nakajima K, Parnavelas J, Hanashima C

    Presentation date： 2011.08

  • Molecular Control of Cell Fate Specification in the Mammalian Brain.

    Carina Hanashima  [Invited]

    Neurogenesis 2011. 

    Presentation date： 2011.06

  • The role of Robo1 in the migration and morphological development of neocortical pyramidal neurons

    Gonda Y, Andrews W, Tabata H, Namba T, Nakajima K, Parnavelas J, Kohsaka S, Uchino S, Hanashima C  [Invited]

    Cortical Development Conference 2011 

    Presentation date： 2011.05

  • Foxg1 regulates the onset of projection neuron production in the neocortex.

    Kumamoto T, Toma K, Mizutani K, Hanashima C

    Cortical Development Conference 2011 

    Presentation date： 2011.05

  • Requirement of GABAergic interneurons and subplate neurons in neocortical arealization.

    Bullmann T, Hanashima C

    44th Annual Meeting of the Japanese Society of Developmental Biologists 

    Presentation date： 2011.05

  • Foxg1 regulates the onset of projection neuron production in the neocortex.

    Kumamoto T, Toma K, Mizutani K, Hanashima C

    44th Annual Meeting of the Japanese Society of Developmental Biologists 

    Presentation date： 2011.05

  • Molecular identity of temporal neuronal precursors in the mouse neocortex.

    BMB2010 

    Presentation date： 2010.12

  • A screen for molecules that determine the specification of cortical upper-layer glutamatergic neurons

    BMB2010 

    Presentation date： 2010.12

  • Molecular identity of temporal neuronal precursors in the mouse neocortex.

    Neuro2010 

    Presentation date： 2010.09

  • Robo1 regulates the morphological development of pyramidal neurons in mouse neocortex

    Gonda、 Yuko, Hanashima, C

    Neuro2010 

    Presentation date： 2010.09

  • Temporal and Spatial Control of Neuronal Identity in the Brain.

    Carina Hanashima  [Invited]

    Presentation date： 2009.08

  • Foxg1 suppresses early cortical cell fate

    Carina Hanashima

    Gordon Research Conference on Neural Development 

    Presentation date： 2004

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Specific Research

  • 大脳皮質知覚神経回路形成における領野の階層決定機構

    2018  

    　View Summary

    大脳皮質は共通の投射標的をもつ６層のニューロンを領野ごとに修飾し、複雑かつ秩序だった３次元の神経回路をつくることで、視覚や体性感覚などの高度な情報処理を担っている。知覚神経回路の形成には細胞内の遺伝子プログラムと末梢感覚器官からの神経入力が必要であると考えられているが、双方の寄与については未だ不明な点が多く残されている。これらの背景をふまえ、本課題では大脳皮質の領野特異的なニューロンの分化を制御する内因性・外因性機構に焦点をあてることで知覚神経回路が構築されるメカニズムを明らかにすることを目的としている。具体的に大脳皮質神経幹細胞が増殖期から分化期に移行するタイミングで一過的に発現上昇するbHLH遺伝子に着目し、時系列の異なる細胞群の抽出を行うために誘導型Cre組み換え酵素のノックインマウスを用い、Creの時期特異的活性化による層特異的ニューロンの標識手法を確立した。特に同一時間に生み出されるニューロンの動態を可視化することで、細胞移動から樹状突起形成までの過程を四次元的に捉え、これまで関連性が不明であった胎生期における神経前駆細胞と分化後の領野特性の発現を直接的に検証することが可能となった。さらに知覚神経回路において感覚入力を担う層ニューロンの分化を制御する転写制御ネットワークを同定し、内因性プログラムによる層および領域特異的なニューロンの分化および統合を制御する分子群を同定した。これら一連の遺伝学的アプローチおよび細胞系譜解析により、同一時間に生み出されるニューロンのダイナミクス、細胞特性、領野の統合パターンを解析することで、大脳皮質領野の階層決定機構の一端が明らかになった。

  • 大脳皮質領野の境界形成メカニズム

    2017  

    　View Summary

    哺乳類特有の脳組織である大脳新皮質は高度な知覚や随意運動を担い、ヒトの精神活動の基盤をなしている。本研究では哺乳類間で高度に保存された運動野と体性感覚野の境界に焦点をあてて、第４層ニューロンの分化と統合ダイナミクスを解析することで、大脳皮質領野の形成機構を明らかにすることを目的とした。これまで最初に誕生するカハールレチウス細胞から第５/６層の深層ニューロンへの産生切り替えを担う転写因子Foxg1が、大脳皮質形成後期の上層ニューロンにおいてCOUP-TF遺伝子と相補的な発現を示すことを見出した。さらにトランスクリプトームとChIP-Seq解析により、Foxg1とCOUP-TF間の相互作用が大脳皮質の第４層ニューロンの分化決定を制御している可能性を見出した。これらの知見を生体内で検証するために、ノックアウトマウス系統を用いたFoxg1 - COUP-TF1の動態解析、機能獲得および機能喪失実験を行ったところ、両者の相補的な発現が第４層のニューロンの分化を規定していることを明らかにした。

 

Syllabus

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Teaching Experience

  • Master's Thesis (Department of Interfrative Bioscience and Biomedecal Engineering)

    早稲田大学大学院先進理工学研究科  

  • Developmental Biology

    早稲田大学大学院先進理工学研究科  

  • 修士論文（生命理工）

    早稲田大学大学院先進理工学研究科  

  • Integrative Biocince and Biomedical Engineering B

    早稲田大学大学院先進理工学研究科  

  • Research on Developmental Biology

    早稲田大学大学院先進理工学研究科  

  • 発生生物学研究

    早稲田大学大学院先進理工学研究科  

  • 発生生物学持論

    早稲田大学大学院先進理工学研究科  

  • 総合生命理工学持論

    早稲田大学大学院先進理工学研究科  

  • 海洋生物学

    早稲田大学教育学部  

  • 発生学

    早稲田大学教育学部  

  • 遺伝生物学

    早稲田大学教育学部  

  • 発生神経生物学

    大阪大学基礎工学部  

  • 組織学各論

    神戸大学医学部  

  • 生体防御科学特論

    奈良女子大学大学院  

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Social Activities

  • CDB学生主催セミナー

    理化学研究所 

    2012
    -
    2017.03

  • RIKEN Joint Retreat オーガナイザー

    2011
    -
    2017

  • Editorial Board

    Frontiers in Neuroscience 

    2016.11
    -
    　

  • Senior Editor

    Brain Research 

    2016.03
    -
    　

  • International Advisory Board

    Journal of the Medical Sciences 

    2015.11
    -
    　

  • 日本発生生物学会

    2012.04
    -
    　

  • 日本分子生物学会

    2010.10
    -
    　

  • 日本神経科学

    2009.07
    -
    　

  • Society for Neuroscience

    2005.05
    -
    　

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