Our Research

Recent Publications

REVIEW ARTICLE

Front. Cell. Neurosci., 28 January 2015http://dx.doi.org/10.3389/fncel.2014.00473

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 is important for achieving a better understanding of neocortical development and evolution.

Neurogenin2-d4Venus and Gadd45g-d4Venus transgenic mice: Visualizing mitotic and migratory behaviors of cells committed to the neuronal lineage in the developing mammalian brain

Development, Growth & Differentiation 56, 293-304, 2014

 

To achieve highly sensitive and comprehensive assessment of the morphology and dynamics of cells committed to the neuronal lineage in mammalian brain primordia, we generated two transgenic mouse lines expressing a destabilized (d4) Venus controlled by regulatory elements of the Neurogenin2 (Neurog2) or Gadd45g gene. In mid-embryonic neocortical walls, expression of Neurog2-d4Venus mostly overlapped with that of Neurog2 protein, with a slightly (1 h) delayed onset. Although Neurog2-d4Venus and Gadd45g-d4Venus mice exhibited very similar labeling patterns in the ventricular zone (VZ), in Gadd45g-d4Venus mice cells could be visualized in more basal areas containing fully differentiated neurons, where Neurog2-d4Venus fluorescence was absent. Time-lapse monitoring revealed that most d4Venus+ cells in the VZ had processes extending to the apical surface; many of these cells eventually retracted their apical process and migrated basally to the subventricular zone, where neurons, as well as the intermediate neurogenic progenitors that undergo terminal neuron-producing division, could be live-monitored by d4Venus fluorescence. Some d4Venus+ VZ cells instead underwent nuclear migration to the apical surface, where they divided to generate two d4Venus+ daughter cells, suggesting that the symmetric terminal division that gives rise to neuron pairs at the apical surface can be reliably live-monitored. Similar lineage-committed cells were observed in other developing neural regions including retina, spinal cord, and cerebellum, as well as in regions of the peripheral nervous system such as dorsal root ganglia. These mouse lines will be useful for elucidating the cellular and molecular mechanisms underlying development of the mammalian nervous system.

 

Ferret-mouse differences in interkinetic nuclear migration and cellular densification in the neocortical ventricular zone.  

Neuroscience Research 83, 25-32, 2014

 

The thick outer subventricular zone (OSVZ) is characteristic of the development of human neocortex. How this region originates from the ventricular zone (VZ) is largely unknown. Recently, we showed that over-proliferation–induced acute nuclear densification and thickening of the VZ in neocortical walls of mice, which lack an OSVZ, causes reactive delamination of undifferentiated progenitors and invasion by these cells of basal areas outside the VZ. In this study, we sought to determine how VZ cells behave in non-rodent animals that have an OSVZ. A comparison of mid-embryonic mice and ferrets revealed: (1) the VZ is thicker and more pseudostratified in ferrets. (2) The soma and nuclei of VZ cells were horizontally and apicobasally denser in ferrets. (3) Individual endfeet were also denser on the apical (ventricular) surface in ferrets. (4) In ferrets, apicalward nucleokinesis was less directional, whereas basalward nucleokinesis was more directional; consequently, the nuclear density in the periventricular space (within 16 μm of the apical surface) was smaller in ferrets than in mice, despite the nuclear densification seen basally in ferrets. These results suggest that species-specific differences in nucleokinesis strategies may have evolved in close association with the magnitudes and patterns of nuclear stratification in the VZ.

 

 

TAG-1–assisted progenitor elongation streamlines nuclear migration to optimize subapical crowding. 

Nat. Neurosci. 16, 1556-1566, 2013, DOI: 10.1038/nn.3525   PubMed

 

Neural progenitors exhibit cell cycle–dependent interkinetic nuclear migration (INM) along the apicobasal axis. Despite recent advances in understanding its underlying molecular mechanisms, the processes to which INM contributes mechanically and the regulation of INM by the apicobasally elongated morphology of progenitors remain unclear. We found that knockdown of the cell-surface molecule TAG-1 resulted in retraction of neocortical progenitors' basal processes. Highly shortened stem-like progenitors failed to undergo basalward INM and became overcrowded in the periventricular (subapical) space. Surprisingly, the overcrowded progenitors left the apical surface and migrated into basal neuronal territories. These observations, together with the results of in toto imaging and physical tests, suggest that progenitors may sense and respond to excessive mechanical stress. Although, unexpectedly, the heterotopic progenitors remained stem-like and continued to sequentially produce neurons until the late embryonic period, histogenesis was severely disrupted. Thus, INM is essential for preventing overcrowding of nuclei and their somata, thereby ensuring normal brain histogenesis.

 

Results

・Heterogeneous apicobasal nuclear movements in the VZ

・TAG-1 knockdown induces progenitor shortening

・Shortened progenitors are periventricularly overcrowded

・Overcrowded cells are under excessive mechanical stress

・Overcrowded progenitors delaminate and form heterotopia

・Heterotopia maintains cytogenesis but disrupt histogenesis

 

Discussion

 

・TAG-1 and progenitors' histogenetic behaviors

・Morphology-based and synecological understanding of INM

・Mechanics underlying progenitors' behaviors

・Robust cytogenesis by shortened and heterotopic progenitors

 

 

Ongoing Research Project:

 

Neurogenesis regulated through three-dimensional cellular movement and cell-cell interactions within the neuroepithelium

Supported by Grant-in-Aid for Scientific Research on Innovative Areas (Cross-talk between moving cells and microenvironment as a basis of emerging order in multicellular system, FY2010-2014

 

The neural tube and the walls of the early embryonic brain vesicles are composed entirely of undifferentiated progenitor cells and are referred to collectively as the neuroepithelium (NE). Structurally, the NE is pseudostratified; that is, although there may be up to ten layers of nuclei, the cytoplasm of each cell extends to contact both the apical and basal surfaces of the wall, resulting in a bipolar cellular morphology up to 100 μm in length. Progenitor cells are born at the apical surface of the NE, and their nuclei move toward the basal side of the NE during G1 of the cell cycle. After completing S-phase in the basal portion of the NE, the nuclei return to the apical surface, where they undergo division as their parent cells did. Thus, the location of any given progenitor cell during this interkinetic nuclear migration (INM) reflects the age of the cell or its degree of progression through the cell cycle. In this project, we will carefully observe cells within the NE, focusing on the relationship between cells differing in age, cell cycle status, and migration direction, and will perform functional experiments to manipulate cell-cell interactions. The goal of this project is to understand the significance of INM and pseudostratification in ordered neurogenesis.

 

 

Previous Researches 

 

Migration, early axonogenesis, and Reelin-dependent layer-forming behavior of early/posterior-born Purkinje cells in the developing mouse lateral cerebellum. Neural Dev. 5, 23 (2010)

 

Purpose

How the young Purkinje cells migrate and initiate the layer formation in response to Reelin in the developing cerebellum? Although the dependence of Purkinje cells’ layer formation on the secreted protein Reelin is well known and a prevailing model suggests that Purkinje cells migrate along the “radial glial” fibers connecting the ventricular and pial surfaces, it is not clear how Purkinje cells behave in response to Reelin to initiate their layer. Furthermore, it is not known what nascent Purkinje cells look like in vivo. When and how Purkinje cells start axonogenesis must also be elucidated.

Results

We found that Purkinje cells generated on embryonic day (E) 10 in the developing mouse cerebellum migrate tangentially towards the anterior, exhibiting an elongated morphology consistent with axonogenesis at E12. After their somata reach the outer/dorsal region by E13, they change “posture” by E14 through remodeling of non-axon (dendrite-like) processes and a switchback-like mode of somal movement towards a superficial Reelin-rich zone, while their axon-like fibers remain relatively deep, which demarcates the somata-packed portion as a plate (called the Purkinje plate). In the cerebellum of reelermice, which suffer from ataxic gait due to abnormal cerebellar cortical histogenesis, the early born posterior lateral Purkinje cells are initially normal during migration with anteriorly-extended axon-like fibers until E13, but then fail to form the plate due to the lack of the posture-change step. This is the first demonstration of the beginning of layer formation by Purkinje cells (summarized in the figure, published in Neural Development [2010] and selected as a “highly accessed paper”). This study provides a solid basis for further elucidation of Reelin’s function and the mechanisms underlying the cerebellar corticogenesis, and will contribute to the understanding of how polarization of individual cells drives the overall brain morphogenesis. Our finding is relevant to future efforts to reconstruct the Purkinje cells layer in the cerebellum affected by degenerative diseases.

 

 

 

Rac is involved in the interkinetic nuclear migration of cortical progenitor cells. Neurosci. Res.63, 294-301 (2009)

 

Purpose

In the developing brain wall, neural progenitor cells exhibit nuclear migration during their cell cycle progression. After completing S phase in the basal (pial) side of the neuroepithelium or ventricular zone (VZ), their nuclei go to the apical (ventricular) surface of the VZ, where they undergo division. The nuclei of cells newly born at the apical surface of the VZ move toward the basal side during G1 phase of the cell cycle. This to-and-fro nuclear/somal movement or interkinetic nuclear migration (INM) was first suggested by Sauer in 1935 and was experimentally proven by pulse-and-chase experiments based on 3H-thymidine labeling. Our group previously established a time-lapse monitoring system of INM (Neuron, 2001). Although INM seems to be important for proper cytogenesis, the molecular mechanisms that underlie INM are not well understood. The small GTPase Rac functions in a number of cellular processes, including cytoskeletal regulation, cell-cell adhesion, and migration. Recent three-dimensional functional studies in the developing brain have shown that Rac regulates migration of neurons and extension of neuronal processes. Based on the function of Rac in neurons that exhibit dynamic morphological changes, we reasoned that Rac might also work in progenitor cells, which show highly dynamic behavior, such as INM and cell division. Involvement of Rac in INM has not yet been directly assessed at the single-cell level.

Results

 By cross-sectional and orthogonal immunofluorescence examination, we found that Rac1 is expressed in mid-embryonic mouse telencephalic progenitor cells. Localization is marked at the apical endfoot. Pharmacological inhibition of Rac in slice cultures during the adventricular phase of INM retards nucleokinesis and results in unsuccessful cytokinesis at the apical surface. Similar results were obtained by introducing a dominant-negative form of Rac1. These results suggest that Rac may play a role in INM in the developing mouse brain (Neuroscience Research, 2009).

 

 

 

 Periventricular Notch activation and asymmetric Ngn2 and Tbr2 expression in pair-generated neocortical daughter cells. Mol. Cell. Neurosci. 40, 225-233 (2009)

 

Purpose

Formation of the neocortex relies on the precise balance between neurogenesis and maintenance of a neural progenitor pool in the pallial primordium during embryonic development. The mechanism of this asymmetric daughter-cell production by the progenitor population has been extensively studied, but is still not fully understood In order to elucidate the intrinsic and extrinsic mechanisms regulating the asymmetric cell output of progenitor cells, a careful analysis of the spatiotemporal expression patterns of factors controlling cell fate is needed. Especially, how Notch is activated in neural progenitor cells and their daughter cells and how Notch ligand such as Delta-like 1 (Dll1) is expressed need to be elucidated. We previously found that differentiation of progenitor cells towards the neuronal lineage is regulated by Neurogenin2 (Ngn2) (Development, 2004). Then, Tbr2 was reported to be also important for the commitment to the neuronal lineage. Therefore, we extended our analysis to ask how nascent daughter cells start expressing Ngn2, and to determine the relationship between Ngn2 and Tbr2 during the course of lineage commitment of neural progenitor cells.

Results

Through collaboration with Dr. Yoon Kong (Pohang University of Science and Technology), we found that neural progenitor cells committed to the neuronal lineage expresse the Notch-ligand Delta-like 1 (Dll1). Further, our time-lapse observation directly showed that progenitor cells whose Notch activation is reduced by conditional knock-out of Mind bomb-1 (Mib1), an essential component of Notch ligand endocytosis, failed to maintain undifferentiated progenitor pool, leading to premature neuronal differentiation (Neuron, 2008). To track the developmental time course of Ngn2 and Tbr2 expression in VZ cells, time-lapse observation was performed on daughter cells of individually DiI-labeled progenitor cells in cultured neocortical slices, followed by immunostaining for Ngn2 or Tbr2. We found that Ngn2 protein expression was initiated asymmetrically in the surface-generated daughter cells as early as 2 h after birth, about 2 h earlier than the onset of Tbr2 expression. Luciferase and ChIP assays further revealed that Tbr2 is directly downstream of Ngn2. Daughter cells expressing Ngn2 or Tbr2 were connected to the ventricular surface and maintained expression of the two transcription factors after detaching from the ventricular surface. Inhibition of Notch signaling in nascent surface-born daughter cells by treatment with a γ-seceretase inhibitor strikingly increased the frequency of Ngn2 expression in daughter cells 2 h after birth. Activation of Notch was observed not only in the basal VZ, but also in the periventricular VZ containing nascent daughter cells. These results suggest that the periventricular area and the initial morphology of surface-born daughter cells may be important for the regulation of cell fate choice. (Molecular Cellular Neuroscience, 2009).

 

 

Publications (2004~, Miyata lab @ Nagoya)

Okamoto, M., Shinoda, T., Kawaue, T., Nagasaka, A., Miyata, T. Ferret-mouse differences in interkinetic nuclear migration and cellular densification in the neocortical ventricular zone. Neurosci. Res. 83, 25-32, 2014

PubMed

 

Kawaue T, Sagou K, Kiyonari H, Ota K, Okamoto M, Shinoda T, Kawaguchi A, Miyata T. Neurogenin2-d4Venus and Gadd45g-d4Venus transgenic mice: Visualizing mitotic and migratory behaviors of cells committed to the neuronal lineage in the developing mammalian brain. Dev Growth Differ. 56, 293-304, 2014

PubMed

 

Namba, T., Kibe, Y., Funahashi, Y., Nakamuta, S., Takano, T., Ueno, T., Shimada, A., Kozawa, S., Okamoto, M., Shimoda, Y., Oda, K., Wada, Y., Masuda, T., Sakakibara, A., Igarashi, M., Miyata, T., Faivre-Sarrailh, C., Takeuchi, K., Kaibuchi, K. Pioneering axons regulate neuronal polarization in the devveloping cerebral cortex. Neuron 81, 814-829, 2014

PubMed

 

Ageta-Ishihara, N., Miyata, T., Ohshima, C., Watanabe, M., Sato, Y., Hamamura, Y., Higashijima, T., Mazitschek, R., Bito, H., Kinoshita, M. Septins promote dendrite and axon development by negatively regulating microtubule stability via HDAC6-mediated deacetylation. Nat. Commun. 4: 2532, DOI: 10.1038/ncomms3532

PubMed

 

Okamoto, M., Namba, T., Shinoda, T., Kondo, T., Watanabe, T., Inoue, Y., Takeuchi, K., Enomoto, Y., Ota, K., Oda, K., Wada, Y., Sagou, K., Saito, K., Sakakibara, A., Kawaguchi, A., Nakajima, K., Adachi, T., Fujimori, T., Ueda, M. Hayashi, S., Kaibuchi, K., Miyata, T. TAG-1–assisted progenitor elongation streamlines nuclear migration to optimize subapical crowding. Nat. Neurosci.,16: 1556-1566 (2013) DOI: 10.1038/nn.3525

PubMed

 

Sakakibara, A., Ando, R., Sapir, T., Tanaka, T. Microtubule dynamics in neuronal morphogenesis. (2013) Open Biol. 3:130061 DOI: 10.1098/rsob.130061

PubMed

 

Sapir, T., Levy, T., Sakakibara, A., Rabinkov, A., Miyata, T., Reiner, O. Shootin1 acts in concert with KIF20B to promote polarization of migrating neurons. (2013) J. Neurosci. 33:11932-11948 DOI: 10.1523/JNEUROSCI.5425-12.2013

PubMed

 

Wu, J Liu, L Matsuda, T , Zao, YRebane, A Drobizhev, M Chang, Y-F Araki, S Arai, Y March, K Thomas, HESagou, K , Miyata, TNagai, T , Li, W-H , and Campbell, RE  Improved orange and red Ca2+ indicators and photophysical considerations for optogenetic applications. ACS Chem. Neurosci. (2013.3.1 on line)DOI: 10.1021/cn400012b

PubMed

 

Sakakibara, A.(corresponding author), Sato, T., Ando, R., Noguchi, N., Masaoka, M., Miyata, T. Dynamics of centrosome translocation and microtubule organization in neocortical neurons during distinct modes of polarization.Cereb. Cortex 2013 Jan 10. (doi:10.1093/cercor/bhs411)

PubMed

 

Xie, M.-J., Yagi, H., Kuroda, K., Wang, C.-C., Komada, M., Zhao, H., Sakakibara, A., Miyata, T. Nagata, K., Iguchi, T., Sato, M. WAVE2-Abi2 complex controls growth cone activity and regulates the multipolar-bipolar transition as well as the initiation of glia-guided migration. Cereb. Cortex 23:1410-1423 (2013) (doi: 10.1093/cercor/bhs123)

PubMed

 

Pérez-Martínez, F.J., Luque-Río, A., Sakakibara, A., Hattori, M., Miyata, T., Luque, J. M. Reelin-dependent ApoER2 downregulation uncouples newborn neurons from progenitor cells. Biol. Open 1:1258-1263 (2012) 

PubMed

 

Nakamuta, S., Funahashi, Y., Namba, T., Arimura, N., Picciotto, M.R., Tokumitsu, H., Soderling, T.R., Sakakibara, A., Miyata, T., Kamiguchi, H., Kaibuchi, K. Local application of neurotrophins specifies axons through inositol 1,4,5-trisphosphate, calcium, and ca2+/calmodulin-dependent protein kinases. Sci. Signal. 4(199):ra76 (2011)

PubMed

 

Natsume, S., Kato, T., Kinjo, S., Enomoto, A., Toda, H., Shimato, S., Ohka, F., Motomura, K., Kondo, Y., Miyata, T., Takahashi, M., Wakabayashi, T. Girdin maintains the stemness of glioblastoma stem cells. Oncogene 312715-2724 (2011)

PubMed

 

Miyata, T., Ono Y, Okamoto M, Masaoka M, Sakakibara A, Kawaguchi A, Hashimoto M, Ogawa M. Migration, early axonogenesis, and Reelin-dependent layer-forming behavior of early/posterior-born Purkinje cells in the developing mouse lateral cerebellum. Neural Dev. 5, 23 (2010) 

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PubMed

 

Miyata, T., Kawaguchi, D., Kawaguchi, A., Gotoh, Y. Mechanisms that regulate the number of neurons during mouse neocortical development. Curr. Opin. Neurobiol. 20, 22-28 (2010)

PubMed

 

Kato TM, Kawaguchi A, Kosodo Y, Niwa H, *Matsuzaki F.

 Lunatic fringe potentiates Notch signaling in the developing brain. Mol Cell Neurosci. 45, 12-25, 2010

PubMed

 

Uchida T, Baba A, Perez-Martinez FJ, Hibi T, Miyata T, Luque JM, Nakajima K, Hattori M. Downregulation of functional Reelin receptors in projection neurons implies that primary Reelin action occurs at early/premigratory stages. J Neurosci. 29:10653-62 (2009)

PubMed

 

Saito K, Dubreuil V, Arai Y, Wilsch-Brauninger M, Schwudke D, Saher G, Miyata T, Breier G, Thiele C, Shevchenko A, Nave KA, Huttner WB. Ablation of cholesterol biosynthesis in neural stem cells increases their VEGF expression and angiogenesis but causes neuron apoptosis. Proc Natl Acad Sci U S A 106(20):8350-5 (2009)

PubMed

 

Minobe, S., Sakakibara, A., Ohdachi, T., Kanda, R., Kimura, M., Nakatani, S., Tadokoro, R., Ochiai, W., Nishizawa, Y., Mizoguchi, A., Kawauchi, T., Miyata, T.: Rac is involved in the interkinetic nuclear migration of cortical progenitor cells. Neurosci. Res. 63, 294-301 (2009)

PubMed

 

Ochiai, W.,* Nakatani, S.,* Takahara, T., Kainuma, M., Masaoka, M., Minobe, S., Namihira, M., Nakashima, K., Sakakibara, A., Ogawa, M., Miyata, T.: Periventricular Notch activation and asymmetric Ngn2 and Tbr2 expression in pair-generated neocortical daughter cells. Mol. Cell. Neurosci. 40, 225-233 (2009) (*Equal contribution)

PubMed

 

Yoon, K.-J., Koo, B.-K., Jeong, H.-W., Ghim, J., Kwon, M.-C., Moon, J.-S., Miyata, T.Kong, Y.-Y.: Mind bomb 1-experssing intermediate progenitors generate Notch signaling to maintain radial glial cells. Neuron 58, 519-531 (2008)

PubMed

 

Sunabori, T., Tokunaga, A., Nagai, T., Sawamoto, K., Okabe, M., Miyawaki, A., Matsuzaki, Y., Miyata, T., Okano, H.: Cell-cycle-specific nestin expression coordinates with morphological changes in embryonic cortical neural progenitors. J. Cell Sci. 121, 1204-1212 (2008)

PubMed

 

Koyasu T, Kondo M, Miyata K, Ueno S, Miyata T, Nishizawa Y, Terasaki H.  Photopic electroretinograms of mGluR6-deficient mice. Curr Eye Res. 33, 91-99 (2008) 

PubMed

 

Miyata, T.: Development of three-dimensional architecture of the neuroepithelium: Role of pseudostratification and cellular 'community'. Dev. Growth Differ. 50, S105-S112 (2008)

PubMed

 

Sakaue-Sawano, A., Kurokawa, H., Morimura, T., Hanyu, A., Hama, H., Osawa, H., Kashiwagi, S., Fukami, K., Miyata, T., Miyoshi, H., Imamura, T., Ogawa, M., Masai, H. and Miyawaki, A.: Visualizing spatiotemporal dynamics of multicellular cell-cycle progression. Cell 132, 487-498 (2008).

PubMed

 

Konno, D., Shioi, G., Shitamukai, A., Mori, A., Kiyonari, H., Miyata, T. and Matsuzaki, F.: Neuroepithelial progenitors undergo LGN-dependent planar divisions to maintain self-renewability during mammalian neurogenesis. Nat. Cell Biol. 10, 93-101 (2008)

PubMed

 

Nishizawa, Y., Imafuku, H., Saito, K., Kanda, R., Kimura, M., Minobe, S., Miyazaki, F., Kawakatsu, S., Masaoka, M., Ogawa, M. and Miyata, T.: Survey of the morphogenetic dynamics of the ventricular surface of the developing mouse cortex. Dev. Dyn.  236, 3061-3070 (2007)

PubMed

 

Tamai, H., Shinohara, H., Miyata, T., Saito, K., Nishizawa, Y., Nomura, T. and Osumi, N.: Pax6 transcription factor regulates interkinetic nuclear movement in cortical progenitor cells via centrosomal stabilization. Genes Cells 12, 983-996 (2007)

PubMed

 

Miyata, T.: Morphology and mechanics of daughter cells "delaminating" from the ventricular zone of the developing neocortex. Cell Adh. Migr. 1, 99-101(2007)

PubMed

 

Miyata, T.and Ogawa, M.: Twisting of neocortical progenitor cells underlies a spring-like mechanism for daughter cell migration. Curr.Biol. 17, 146-151 (2007)

PubMed

 

Ochiai, W., Minobe, S., Ogawa, M., Miyata, T.: Transformation of pin-like ventricular zone cells into cortical neurons. Neurosci. Res. 57, 326-329 (2007)

PubMed

 

Miyata, T.: Asymmetric cell division during brain morphogenesis. Prog. Mol. Subcell. Biol. 452, 121-142 (2007)

PubMed

 

Hirai, S., Cui, DF., Miyata, T., Ogawa, M., Kiyonari, H., Suda, Y., Aizawa, S., Banda, Y. and Ohno, S.: The c-Jun N-terminal kinase activator dual leucine zipper kinase regulates axon growth and neuronal migration in the developing cerebral cortex. J. Neurosci. 26, 11992-12002 (2006)

PubMed

 

Imai, F., Hirai, S., Akimoto, K., Koyama, H., Miyata, T., Ogawa, M., Noguchi, S., Sasaoka, T., Noda, T., and Ohno, S.: Inactivation of aPKCλ results in the loss of adherens junctions in neuroepithelial cells without affecting neurogenesis in mouse neocortex. Development 133, 1735-1744 (2006)

PubMed

 

Mutoh, T., Miyata, T., Kashiwagi, S., Miyawaki, A., and Ogawa, M.: Dynamic behavior of individual cells in developing organotypic brain slices revealed by the photoconvertable protein Kaede. Exp. Neurol. 200, 430-437 (2006)

PubMed

 

Naruse, M., Nakahira, E., Miyata, T., Hitoshi, S., Ikenaka, K., and Bansai, R.: Induction of oligodendrocyte progenitors in dorsal forebrain by intraventricular microinjection of FGF-2. Dev. Biol. 60, 1084-1100 (2006)

PubMed

 

Zou, P., Muramatsu, H., Miyata, T., and Muramatsu, T.: Midkine, a heparin-binding growth factor, is expressed in neural precursor cells and promotes their growth. J. Neurochem. 99, 1470-1479 (2006)

PubMed

 

Miyata, T., Saito, K., Nishizawa, Y., Murayama, A., Masaoka, M., and Ogawa, M.: Modern slice culture for direct observation of production and migration of brain neurons. Nagoya J. Med. Sci. 67, 65-70 (2005)

PubMed

 

Ueno S, Kondo M, Miyata K, Hirai T, Miyata T, Usukura J, Nishizawa Y, Miyake Y. Physiological function of S-cone system is not enhanced in rd7 mice.  Exp Eye Res. 81, 751-758 (2005) 

PubMed

 

Uematsu J, Nishizawa Y, Hirako Y, Kitamura K, Usukura J, Miyata T, Owaribe K. Both type-I hemidesmosomes and adherens-type junctions contribute to the cell-substratum adhesion system in myoepithelial cells. Eur J Cell Biol. 84, 407-415 (2005) 

PubMed

 

Kawaguchi, A., Ogawa, M., Saito, K., Matsuzaki, F., Okano, H., and Miyata, T.: Differential expression of Pax6 and Ngn2 between pair-generatged cortical neurons. J. Neurosci. Res. 78, 784-795 (2004)

PubMed

 

Miyata, T., Kawaguchi, A., Saito, K., Kawano, M., Muto, T., and Ogawa, M.: Asymmetric production of surface-dividing and non-surface-dividing cortical progenitor cells. Development 131, 3133-3145 (2004)

PubMed

 

Saito, K., Kawaguchi, A., Kashiwagi, S., Yasugi, S., Ogawa, M., and Miyata, T.: Morphological asymmetry in dividing retinal progenitor cells. Develop. Growth & Differ. 45, 219-229 (2003)

PubMed

 

Shinozaki, K., Miyagi, T., Yoshida, M., Miyata, T., Ogawa, M., Aizawa, S., and Suda, Y.: Absence of Cajal-Retzius cells and subplate neurons associated with defects of tangential migration from ganglionic eminence in Emx1/2 double mutant cerebral cortex. Development 129, 3479-3492 (2002)

PubMed

 

Miyata, T., Kawaguchi, A., Saito, K., Kuramochi, H., and Ogawa, M.: Visualization of cell cycling by an improvement in slice culture methods. J. Neurosci. Res.69, 861-868 (2002)

PubMed

 

Ogawa Y, Sawamoto K, Miyata,T., Miyao S, Watanabe M, Nakamura M, Bregman BS, Koike M, Uchiyama Y, Toyama Y, Okano H.: Transplantation of in vitro-expanded fetal neural progenitor cells results in neurogenesis and functional recovery after spinal cord contusion injury in adult rats. J. Neurosci. Res. 69, 925-933 (2002).

PubMed

 

Takasawa K, Kitagawa K, Yagita Y, Sasaki T, Tanaka S, Matsushita K, Ohstuki T, Miyata T, Okano H, Hori M, Matsumoto M. Increased proliferation of neural progenitor cells but reduced survival of newborn cells in the contralateral hippocampus after focal cerebral ischemia in rats. J. Cereb. Blood Flow Metab. 22, 299-307 (2002).

PubMed

 

Yagita Y, Kitagawa K, Sasaki T, Miyata, T., Okano H, Hori M, Matsumoto M. Differential expression of Musashi1 and nestin in the adult rat hippocampus after ischemia. J. Neurosci. Res. 69, 750-756 (2002).

PubMed

 

Yamazaki, Y., Makino, H., Hamaguchi-Hamada, K., Hamada, S., Sugino, H., Kawase, E., Miyata, T., Ogawa, M., Yanagimachi. R., and Yagi, T.: Assessment of the developmental totipotency of neural cells in the cerebral cortex of mouse embryo by nuclear transfer. Proc. Natl. Acad. Sci. USA S 98, 14022-14026 (2001)

PubMed

 

Miyata, T., Kawaguchi, A., Okano, H., and Ogawa, M. Asymmetric inheritance of radial glial fibers by cortical neurons. Neuron 31, 727-741 (2001)

PubMed

 

Kawaguchi, A., Miyata, T., Sawamoto, K., Takashita, N., Murayama, A., Akamatsu, W., Ogawa, M., Okabe, M., Tano, Y., Goldman, S.A., and Okano, H. Nestin-EGFP mice: visualization of the self-renewal and multipotency of CNS stem cells. Mol. Cell. Neurosci. 17, 259-273 (2001)

PubMed

 

Yagita, Y., Kitagawa, K., Otsuki, T., Kuwabara, K., Mabuchi, T., Miyata, T., Okano, H., Hori, M., and Matsumoto, M.: Proliferation of neuronal progenitor cells and increased neurogenesis in the ischemic adult rat hippocampus. Stroke 32, 1890-1896 (2001)

PubMed

 

Kaneko, Y., Sakakibara, S., Imai, T., Suzuki, A., Nakamura, Y., Sawamoto, K., Ogawa, Y., Toyama, Y., Miyata, T., and Okano, H.: Musashi1: an evolutionally conserved marker for CNS progenitor cells including neural stem cells. Dev. Neurosci. 22, 139-153 (2000)

PubMed

 

Nakamura, Y., Sakakibara, S., Miyata, T., Ogawa, M., Shimazaki, T., Weiss, S., Kageyama, R., and Okano, H.: The bHLH gene Hes1 as a repressor of neuronal commitment of the CNS stem cells. J. Neurosci. 20, 283-293 (2000)

PubMed

 

Ohtani, T., Ishihara, K., Atsumi, T., Nishida, K., Keneko, Y., Miyata, T., Itoh, S., Narimatsu, M., Maeda, H., Fukada, T., Itoh, M., Okano, H., Hibi, T., and Hirano, T.: Dissection of signaling cascade through gp130 in vivo: Reciprocal roles for STAT3-and SHP2-mediated signals in cytokine and immunoglobulin production. Immunity 12, 95-105 (2000)

PubMed

 

Miyata, T., Maeda, T., and Lee, J.E.: NeuroD is required for differentiation of the granule cells in the cerebellum and hippocampus. Genes Dev. 13, 1647-1652 (1999)

PubMed

 

Miyata, T., Nakajima, K., Mikoshiba, K., and Ogawa, M.: Regulation of Purkinje cell alignment by Reelin as revealed with CR-50 antibody. J. Neurosci. 17, 3599-3609 (1997)

PubMed

 

Miyata, T., Nakajima, K., Mikoshiba, K., and Ogawa, M.: Distinct arrangement patterns of Purkinje cells between normal and reeler mice are reproduced in cerebellar explants. Dev. Neurosci. 19, 124 (1997)

 

Del Rio, J., Heimrich, B., Borrell, V., Froster, E., Drakew, A., Alcantara, S., Nakajima, K., Miyata, T., Ogawa, M., Mikoshiba, K., Derer, P., Frotscher, M., and Soriano, E.: A role for Cajal-Retzius cells and reelin in the development of hippocampal connections. Nature 385, 70-74 (1997)

PubMed

 

Nakajima, K., Mikoshiba, K., Miyata, T., Kudo, C., and Ogawa, M.: Disruption of hippocampal development in vivo by CR-50 mAb against Reelin. Proc. Natl. Acad. Sci. USA 94, 8196-8201 (1997)

PubMed

 

De Vergeyck, V., Nakajima, K., Lambert de Rouvroit, C., Naerhuyzen, B., Goffinet, A. M., Miyata, T., Ogawa, M., and Mikoshiba, K.: A truncated Reelin protein is produced but not secreted in the “Orleans” reeler mutation. Mol. Brain Res. 50, 85-90 (1997)

PubMed

 

D’Arcangelo, G., Nakajima, K., Miyata, T., Ogawa, M., Mikoshiba, K., Curran, T.: Reelin is a secreted glycoprotein recognized by the CR-50 monoclonal antibody. J. Neurosci. 17, 23-31 (1997)

PubMed

 

Yoneshima, H., Nagata, E., Matsumoto, M., Yamada, M., Nakajima, K., Miyata, T., Ogawa, M., and Mikoshiba, K.: A novel neurological mutant mouse, yotari, which exhibits reeler-like phenotype but expresses CR-50 antigen/Reelin. Neurosci. Res. 29, 217-223 (1997)

PubMed

 

Miyata, T., Nakajima, K., Aruga, J., Takahashi, S., Ikenaka, K., Mikoshiba, K, and Ogawa, M.: Distribution of a reeler gene-related antigen in the developing cerebellum: an immunohistochemical study with an allogeneic antibody CR-50 on normal and reeler mice. J Comp. Neurol. 372, 215-228 (1996)

PubMed

 

Sakakibara, S., Okano, H., Imai, T., Hamaguchi, K., Aruga, J., Nakajima, K., Nagata, T., Kurihara, Y., Uesugi, S., Miyata, T., Ogawa, M., and Mikoshiba, K.: Mouse-musashi-1, a neural RNA-binding protein highly enriched in the mammalian CNS stem cell. Dev. Biol. 176, 230-242 (1996) 

PubMed

 

Takahashi, S., Yamamoto, H., Matsuda, Z., Ogawa, M., Yagyu, K., Taniguchi, T., Miyata, T., Koda, H., Higuchi, T., Okutani, F., and Fujimoto, S.: Identification of two highly homologous presynaptic proteins distinctly localized at the dendritic and somatic synapses. FEBS letters 368, 455-460 (1995)

PubMed

 

Ogawa, M., Miyata, T., Nakajima, K., Yagyu, K., Ikenaka, K., Yamamoto, H., and Mikoshiba, K.: The reeler gene-associated antigen on Cajal-Retzius neurons is a crucial molecule for laminar organization of cortical neurons. Neuron 14, 899-912 (1995) 

PubMed

 

Miyata, T., and Ogawa, M.: Developmental potentials of early telencephalic neuroepithelial cells: a study with microexplant culture. Dev. Growth & Differ.36, 319-331 (1994)