研究者詳細 - 篠田　友靖

神経幹細胞による「他力」活用査読有り

篠田友靖, 川上巧, 宮田卓樹

生化学 90 巻 ( 6 ) 頁： 820 - 824 2018年12月

Katanin p80, NuMA and cytoplasmic dynein cooperate to control microtubule dynamics. 査読有り

Jin M, Pomp O, Shinoda T, Toba S, Torisawa T, Furuta K, Oiwa K, Yasunaga T, Kitagawa D, Matsumura S, Miyata T, Tan TT, Reversade B, Hirotsune S

Scientific reports 7 巻頁： 39902 2017年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Scientific Reports

Human mutations in KATNB1 (p80) cause severe congenital cortical malformations, which encompass the clinical features of both microcephaly and lissencephaly. Although p80 plays critical roles during brain development, the underlying mechanisms remain predominately unknown. Here, we demonstrate that p80 regulates microtubule (MT) remodeling in combination with NuMA (nuclear mitotic apparatus protein) and cytoplasmic dynein. We show that p80 shuttles between the nucleus and spindle pole in synchrony with the cell cycle. Interestingly, this striking feature is shared with NuMA. Importantly, p80 is essential for aster formation and maintenance in vitro. siRNA-mediated depletion of p80 and/or NuMA induced abnormal mitotic phenotypes in cultured mouse embryonic fibroblasts and aberrant neurogenesis and neuronal migration in the mouse embryonic brain. Importantly, these results were confirmed in p80-mutant harboring patient-derived induced pluripotent stem cells and brain organoids. Taken together, our findings provide valuable insights into the pathogenesis of severe microlissencephaly, in which p80 and NuMA delineate a common pathway for neurogenesis and neuronal migration via MT organization at the centrosome/spindle pole.

DOI： 10.1038/srep39902

Synergistic action of nectins and cadherins generates the mosaic cellular pattern of the olfactory epithelium. 査読有り

Katsunuma S, Honda H, Shinoda T, Ishimoto Y, Miyata T, Kiyonari H, Abe T, Nibu K, Takai Y, Togashi H

The Journal of cell biology 212 巻 ( 5 ) 頁： 561 - 75 2016年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Cell Biology

In the olfactory epithelium (OE), olfactory cells (OCs) and supporting cells (SCs), which express different cadherins, are arranged in a characteristic mosaic pattern in which OCs are enclosed by SCs. However, the mechanism underlying this cellular patterning is unclear. Here, we show that the cellular pattern of the OE is established by cellular rearrangements during development. In the OE, OCs express nectin-2 and N-cadherin, and SCs express nectin-2, nectin-3, E-cadherin, and N-cadherin. Heterophilic trans-interaction between nectin-2 on OCs and nectin-3 on SCs preferentially recruits cadherin via a-catenin to heterotypic junctions, and the differential distributions of cadherins between junctions promote cellular intercalations, resulting in the formation of the mosaic pattern. These observations are confirmed by model cell systems, and various cellular patterns are generated by the combinatorial expression of nectins and cadherins. Collectively, the synergistic action of nectins and cadherins generates mosaic pattern, which cannot be achieved by a single mechanism.

DOI： 10.1083/jcb.201509020

Disrupted-in-schizophrenia 1 regulates transport of ITPR1 mRNA for synaptic plasticity. 査読有り

Tsuboi D, Kuroda K, Tanaka M, Namba T, Iizuka Y, Taya S, Shinoda T, Hikita T, Muraoka S, Iizuka M, Nimura A, Mizoguchi A, Shiina N, Sokabe M, Okano H, Mikoshiba K, Kaibuchi K

Nature neuroscience 18 巻 ( 5 ) 頁： 698 - 707 2015年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Nature Neuroscience

Disrupted-in-schizophrenia 1 (DISC1) is a susceptibility gene for major psychiatric disorders, including schizophrenia. DISC1 has been implicated in neurodevelopment in relation to scaffolding signal complexes. Here we used proteomic analysis to screen for DISC1 interactors and identified several RNA-binding proteins, such as hematopoietic zinc finger (HZF), that act as components of RNA-transporting granules. HZF participates in the mRNA localization of inositol-1,4,5-trisphosphate receptor type 1 (ITPR1), which plays a key role in synaptic plasticity. DISC1 colocalizes with HZF and ITPR1 mRNA in hippocampal dendrites and directly associates with neuronal mRNAs, including ITPR1 mRNA. The binding potential of DISC1 for ITPR1 mRNA is facilitated by HZF. Studies of Disc1-knockout mice have revealed that DISC1 regulates the dendritic transport of Itpr1 mRNA by directly interacting with its mRNA. The DISC1-mediated mRNA regulation is involved in synaptic plasticity. We show that DISC1 binds ITPR1 mRNA with HZF, thereby regulating its dendritic transport for synaptic plasticity.

DOI： 10.1038/nn.3984

Dysbindin-1, a schizophrenia-related molecule, is involved in the regulation of neuronal dendritic development.

Ito H, Morishita R, Shinoda T, Iwamoto I, Sudo K, Okamoto K, Nagata K

Molecular psychiatry 15 巻 ( 10 ) 頁： 969 2010年10月

統合失調症の発症脆弱因子のプロテオミクス的解析

田谷真一郎, 坪井大輔, 篠田友靖, 貝淵弘三

日本プロテオーム学会大会要旨集 2007 巻 ( 0 ) 頁： 53 - 53 2007年

記述言語：日本語出版者・発行元：日本プロテオーム学会（日本ヒトプロテオーム機構）

統合失調症は世界人口の約１%で発病がみられる重篤な精神疾患である。統合失調症患者を対象にした遺伝学的解析から、複数の統合失調症脆弱性因子の変異が発症に密接に関与することが示唆されているが、発症の分子機構は不明である。スコットランドの統合失調症多発家系の遺伝学的解析より、第１染色体と第１１染色体の相互転座部位に位置する遺伝子としてDISC1が報告された。相互転座の保因者ではDISC1の発現レベルが低下していると考えられている。
　我々はDISC1の機能解析をするために、DISC1結合蛋白質の探索を試みた。アフィニティーカラムクロマトグラフィー法により、ラット脳の抽出液からDISC1結合蛋白質を得た。それらを質量分析により解析した結果、100種以上のDISC1結合蛋白質候補を同定した。新規の分子としてKinesin-1、14-3-3ε、Grb2、既知の分子としてNUDEL、LIS1などの複数のDISC1結合蛋白質を同定した。Kinesin-1は微小菅モーターであり、軸索先端へ分子や小胞の輸送を制御している。NUDEL、LIS1、14-3-3εは複合体を形成し神経細胞の移動を制御することが報告されている。Grb2 は神経栄養因子などのシグナル伝達経路でアダプター分子として機能する。我々は、DISC1がKinesin-1とNUDEL複合体またはGrb2を連結することを見出した。ラットの海馬初代培養神経細胞において、DISC1、Kinesin-1、NUDEL複合体、Grb2は、軸索先端部位で共局在していた。DISC1の発現を抑制した神経細胞では、軸索伸長の阻害が確認でき、NUDEL複合体やGrb2の軸索先端への局在化が阻害されていた。また、NUDELやGrb2がそれぞれ軸索伸長に必要であることを見出した。我々の結果は、DISC1が“積み荷”となるNUDEL複合体とGrb2をKinesin-1に連結させる“積み荷受容体”として機能することで、“積み荷”の軸索先端への局在化に関与していることを示唆している。DISC1の発現量が低下した場合、“積み荷”の正しい場所への輸送が不十分になり、神経細胞の発達に障害が生じると予想される。さらに、DISC1結合蛋白質候補の中から、DISC1により輸送を制御される分子の同定を試みる予定である。

DOI： 10.14889/jhupo.2007.0.53.0

CiNii Research

Inhibition of leukemia-associated RhoGEF (LARG) activity by collapsin response mediator protein-2 (CRMP-2) 査読有り

Taya, S; Shinoda, T; Nagai, K; Iwamatsu, A; Matsuura, Y; Kaibuchi, K

MOLECULAR BIOLOGY OF THE CELL 13 巻頁： 53A - 53A 2002年11月

Analyzing the effect of cell rearrangement on Delta-Notch pattern formation

Oguma, T; Takigawa-Imamura, H; Shinoda, T; Ogura, S; Uemura, A; Miyata, T; Maini, PK; Miura, T

PHYSICAL REVIEW E 107 巻 ( 6 ) 頁： 064404 2023年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Physical Review E

The Delta-Notch system plays a vital role in many areas of biology and typically forms a salt and pepper pattern in which cells strongly expressing Delta and cells strongly expressing Notch are alternately aligned via lateral inhibition. In this study, we consider cell rearrangement events, such as cell mixing and proliferation, that alter the spatial structure itself and affect the pattern dynamics. We model cell rearrangement events by a Poisson process and analyze the model while preserving the discrete properties of the spatial structure. We investigate the effects of the intermittent perturbations arising from these cell rearrangement events on the discrete spatial structure itself in the context of pattern formation and by using an analytical approach, coupled with numerical simulation. We find that the homogeneous expression pattern is stabilized if the frequency of cell rearrangement events is sufficiently large. We analytically obtain the balanced frequencies of the cell rearrangement events where the decrease of the pattern amplitude, as a result of cell rearrangement, is balanced by the increase in amplitude due to the Delta-Notch interaction dynamics. Our framework, while applied here to the specific case of the Delta-Notch system, is applicable more widely to other pattern formation mechanisms.

DOI： 10.1103/PhysRevE.107.064404

Dorsal-to-Ventral Cortical Expansion Is Physically Primed by Ventral Streaming of Early Embryonic Preplate Neurons 国際誌

その他リンク： http://harvest.aps.org/v2/journals/articles/10.1103/PhysRevE.107.064404/fulltext

Two-photon microscopic observation of cell-production dynamics in the developing mammalian neocortex in utero. 査読有り

Kawasoe R, Shinoda T, Hattori Y, Nakagawa M, Pham TQ, Tanaka Y, Sagou K, Saito K, Katsuki S, Kotani T, Sano A, Fujimori T, Miyata T

Development, Growth and Differentiation 62 巻 ( 2 ) 頁： 118 - 128 2020年1月

Saito, K; Okamoto, M; Watanabe, Y; Noguchi, N; Nagasaka, A; Nishina, Y; Shinoda, T; Sakakibara, A; Miyata, T

CELL REPORTS 29 巻 ( 6 ) 頁： 1555 - + 2019年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Cell Reports

Embryonic radial glial fibers that guide most neocortical neurons are ventrally deflected near their terminal, contributing to further expansion of the neocortical area. Saito et al. demonstrate that this fiber deflection is induced physically by a previously unrecognized ventral stream of the earliest generated preplate neurons.

DOI： 10.1016/j.celrep.2019.09.075

Lzts1 controls both neuronal delamination and outer radial glial-like cell generation during mammalian cerebral development 査読有り国際誌

Kawaue T., Shitamukai A., Nagasaka A., Tsunekawa Y., Shinoda T., Saito K., Terada R., Bilgic M., Miyata T., Matsuzaki F., Kawaguchi A.

NATURE COMMUNICATIONS 10 巻 ( 1 ) 頁： 2780 - 2780 2019年6月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Nature Communications

In the developing central nervous system, cell departure from the apical surface is the initial and fundamental step to form the 3D, organized architecture. Both delamination of differentiating cells and repositioning of progenitors to generate outer radial glial cells (oRGs) contribute to mammalian neocortical expansion; however, a comprehensive understanding of their mechanisms is lacking. Here, we demonstrate that Lzts1, a molecule associated with microtubule components, promotes both cell departure events. In neuronally committed cells, Lzts1 functions in apical delamination by altering apical junctional organization. In apical RGs (aRGs), Lzts1 expression is variable, depending on Hes1 expression levels. According to its differential levels, Lzts1 induces diverse RG behaviors: planar division, oblique divisions of aRGs that generate oRGs, and their mitotic somal translocation. Loss-of-function of lzts1 impairs all these cell departure processes. Thus, Lzts1 functions as a master modulator of cellular dynamics, contributing to increasing complexity of the cerebral architecture during evolution.

DOI： 10.1038/s41467-019-10730-y

Differences in the Mechanical Properties of the Developing Cerebral Cortical Proliferative Zone between Mice and Ferrets at both the Tissue and Single-Cell Levels 査読有り

Elasticity-based boosting of neuroepithelial nucleokinesis via indirect energy transfer from mother to daughter

Shinoda Tomoyasu, Nagasaka Arata, Inoue Yasuhiro, Higuchi Ryo, Minami Yoshiaki, Kato Kagayaki, Suzuki Makoto, Kondo Takefumi, Kawaue Takumi, Saito Kanako, Ueno Naoto, Fukazawa Yugo, Nagayama Masaharu, Miura Takashi, Adachi Taiji, Miyata Takaki

PLOS BIOLOGY 16 巻 ( 4 ) 2018年4月

Elasticity-based boosting of neuroepithelial nucleokinesis via indirect energy transfer from mother to daughter.

Shinoda T, Nagasaka A, Inoue Y, Higuchi R, Minami Y, Kato K, Suzuki M, Kondo T, Kawaue T, Saito K, Ueno N, Fukazawa Y, Nagayama M, Miura T, Adachi T, Miyata T

PLoS biology 16 巻 ( 4 ) 頁： e2004426 2018年4月

Katanin p80, NuMA and cytoplasmic dynein cooperate to control microtubule dynamics. 査読有り

Jin M, Pomp O, Shinoda T, Toba S, Torisawa T, Furuta K, Oiwa K, Yasunaga T, Kitagawa D, Matsumura S, Miyata T, Tan TT, Reversade B, Hirotsune S.

Scientific reports 7 巻頁： 39902 2017年1月

Synergistic action of nectins and cadherins generates the mosaic cellular pattern of the olfactory epithelium. 査読有り

Katsunuma S, Honda H, Shinoda T, Ishimoto Y, Miyata T, Kiyonari H, Abe T, Nibu K, Takai Y, Togashi H.

J Cell Biol 212 巻頁： 561-575 2016年2月

Nagasaka Arata, Shinoda Tomoyasu, Kawaue Takumi, Suzuki Makoto, Nagayama Kazuaki, Matsumoto Takeo, Ueno Naoto, Kawaguchi Ayano, Miyata Takaki

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY 4 巻 ( NOV ) 頁： 139 2016年

Disrupted-in-schizophrenia 1 regulates transport of ITPR1 mRNA for synaptic plasticity. 査読有り

Tsuboi D, Kuroda K, Tanaka M, Namba T, Iizuka Y, Taya S, Shinoda T, Hikita T, Muraoka S, Iizuka M, Nimura A, Mizoguchi A, Shiina N, Sokabe M, Okano H, Mikoshiba K, Kaibuchi K.

Nat Neurosci. ( 18 ) 頁： 698-707 2015年5月

Interkinetic nuclear migration generates and opposes ventricular-zone crowding: insight into tissue mechanics 査読有り

Miyata, T; Okamoto, M; Shinoda, T; Kawaguchi, A

FRONTIERS IN CELLULAR NEUROSCIENCE 8 巻 ( 8 ) 頁： 473 2015年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Frontiers in Cellular Neuroscience

The neuroepithelium (NE) or ventricular zone (VZ), from which multiple types of brain cells arise, is pseudostratified. In the NE/VZ, neural progenitor cells are elongated along the apicobasal axis, and their nuclei assume different apicobasal positions. These nuclei move in a cell cycle-dependent manner, i.e., apicalward during G2 phase and basalward during G1 phase, a process called interkinetic nuclear migration (INM). This review will summarize and discuss several topics: the nature of the INM exhibited by neural progenitor cells, the mechanical difficulties associated with INM in the developing cerebral cortex, the community-level mechanisms underlying collective and efficient INM, the impact on overall brain formation when NE/VZ is overcrowded due to loss of INM, and whether and how neural progenitor INM varies among mammalian species. These discussions will be based on recent findings obtained in live, three-dimensional specimens using quantitative and mechanical approaches. Experiments in which overcrowding was induced in mouse neocortical NE/VZ, as well as comparisons of neocortical INM between mice and ferrets, have revealed that the behavior of NE/VZ cells can be affected by cellular densification. A consideration of the physical aspects in the NE/VZ and the mechanical difficulties associated with high-degree pseudostratification (PS) is important for achieving a better understanding of neocortical development and evolution.

DOI： 10.3389/fncel.2014.00473