TY - JOUR
T1 - Dynamics of the cell division orientation of granule cell precursors during cerebellar development
AU - Miyashita, Satoshi
AU - Adachi, Toma
AU - Yamashita, Mariko
AU - Sota, Takayuki
AU - Hoshino, Mikio
N1 - Funding Information:
We would like to thank Dr. Ruth Yu (St Jude Children's Research Hospital) for her comments. This work is supported by Grants-in-Aid for Scientific Research (M.H., 15H04268 ), Challenging Exploratory Research (M.H., 15K14337 ), Innovative Areas (M.H., 15H01304 , 16H06528 ) from MEXT , the SRPBS from AMED ( 16dm0107085h0001 ), Naito Foundation , Takeda Foundation , Uehara Foundation , Princess Takamatsu Cancer Research Fund , Intramural Research Grants (M.H., 27-7 , 28-4 ) for Neurological and Psychiatric Disorders of NCNP . KAKENHI (S.M., 15J06259 ).
Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2017/10
Y1 - 2017/10
N2 - The cerebellar granule cell (GC) system provides a good model for studying neuronal development. In the external granule layer (EGL), granule cell precursors (GCPs) rapidly and continuously divide to produce numerous GCs as well as GCPs. In some brain regions, the orientation of cell division affects daughter cell fate, thus the direction of GCP division is related to whether it produces a GCP or a GC. Therefore, we tried to characterize the orientation of GCP division from embryonic to postnatal stages and to identify an environmental cue that regulates the orientation. By visualizing chromatin in EGL GCPs at M-phase, we found that the directions of cell divisions were not random but dynamically regulated during development. While horizontal and vertical divisions were equivalently observed in embryos, horizontal division was more frequently observed at early postnatal stages. Vertical division became dominant at late cerebellar developmental stages. Administration of a SHH inhibitor to cultured cerebellar slices resulted in randomized orientation of cell division, suggesting that SHH signaling regulates the direction of cell division. These results provide fundamental data towards understanding the development of GCs.
AB - The cerebellar granule cell (GC) system provides a good model for studying neuronal development. In the external granule layer (EGL), granule cell precursors (GCPs) rapidly and continuously divide to produce numerous GCs as well as GCPs. In some brain regions, the orientation of cell division affects daughter cell fate, thus the direction of GCP division is related to whether it produces a GCP or a GC. Therefore, we tried to characterize the orientation of GCP division from embryonic to postnatal stages and to identify an environmental cue that regulates the orientation. By visualizing chromatin in EGL GCPs at M-phase, we found that the directions of cell divisions were not random but dynamically regulated during development. While horizontal and vertical divisions were equivalently observed in embryos, horizontal division was more frequently observed at early postnatal stages. Vertical division became dominant at late cerebellar developmental stages. Administration of a SHH inhibitor to cultured cerebellar slices resulted in randomized orientation of cell division, suggesting that SHH signaling regulates the direction of cell division. These results provide fundamental data towards understanding the development of GCs.
KW - Cell division orientation
KW - Cerebellar development
KW - Sonic hedgehog
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U2 - 10.1016/j.mod.2017.06.002
DO - 10.1016/j.mod.2017.06.002
M3 - Article
C2 - 28633908
AN - SCOPUS:85032717513
SN - 0925-4773
VL - 147
SP - 1
EP - 7
JO - Mechanisms of Development
JF - Mechanisms of Development
ER -