Miyashita Satoshi, Adachi Toma, Yamashita Mariko, Sota Takayuki, Hoshino Mikio
Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, Tokyo 187-8502, Japan; Department of Electric Engineering and Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo 169-8555, Japan.
Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, Tokyo 187-8502, Japan; Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, TWIns, Waseda University, Tokyo 162-8480, Japan.
Mech Dev. 2017 Oct;147:1-7. doi: 10.1016/j.mod.2017.06.002. Epub 2017 Jun 17.
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.
小脑颗粒细胞（GC）系统为研究神经元发育提供了一个良好的模型。在外部颗粒层（EGL）中，颗粒细胞前体（GCPs）快速且持续地分裂，产生大量的GC以及GCPs。在一些脑区，细胞分裂的方向会影响子细胞的命运，因此GCP分裂的方向与它产生的是GCP还是GC有关。所以，我们试图描绘从胚胎期到出生后阶段GCP分裂的方向，并确定一种调节该方向的环境线索。通过在有丝分裂期观察EGL中GCPs的染色质，我们发现细胞分裂的方向并非随机，而是在发育过程中受到动态调节。在胚胎中水平分裂和垂直分裂出现的频率相当，但在出生后早期阶段，水平分裂更为常见。在小脑发育后期，垂直分裂占主导地位。向培养的小脑切片中施用SHH抑制剂会导致细胞分裂方向随机化，这表明SHH信号传导调节细胞分裂的方向。这些结果为理解GC的发育提供了基础数据。
