Cell, Molecular and Developmental Biology Program, Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA, 92521, USA.
Neuroscience Program, Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA, 92521, USA.
Sci Rep. 2018 Jan 12;8(1):680. doi: 10.1038/s41598-017-19116-w.
During mammalian cerebellar development, postnatal granule cell progenitors proliferate in the outer part of the External Granule Layer (EGL). Postmitotic granule progenitors migrate tangentially in the inner EGL before switching to migrate radially inward, past the Purkinje cell layer, to achieve their final position in the mature Granule Cell Layer (GCL). Here, we show that the RacGAP β-chimaerin is expressed by a small population of late-born, premigratory granule cells. β-chimaerin deficiency causes a subset of granule cells to become arrested in the EGL, where they differentiate and form ectopic neuronal clusters. These clusters of granule cells are able to recruit aberrantly projecting mossy fibers. Collectively, these data suggest a role for β-chimaerin as an intracellular mediator of Cerebellar Granule Cell radial migration.
在哺乳动物小脑发育过程中,出生后的颗粒细胞祖细胞在外颗粒层(EGL)的外部增殖。有丝分裂后的颗粒前体细胞先在EGL 的内部分化,然后切换为向内侧的放射状迁移,经过浦肯野细胞层,到达成熟的颗粒细胞层(GCL)中的最终位置。在这里,我们发现 RacGAP β-奇美拉蛋白由一小部分晚生、前迁移的颗粒细胞表达。β-奇美拉蛋白缺失会导致一部分颗粒细胞在 EGL 中停滞,在那里它们分化并形成异位神经元簇。这些颗粒细胞簇能够募集异常投射的苔藓纤维。总的来说,这些数据表明β-奇美拉蛋白作为小脑颗粒细胞放射状迁移的细胞内介质的作用。