Laboratory of Cellular and Molecular Neurobiology, Hellenic Pasteur Institute, 127 Vassilissis Sofias Avenue, 11521 Athens, Greece.
Mol Cell Neurosci. 2010 May;44(1):15-29. doi: 10.1016/j.mcn.2010.01.011. Epub 2010 Feb 12.
During nervous system development, neural progenitors arise in proliferative zones, then exit the cell cycle and differentiate as they migrate away from these zones. The neuronal protein BM88/Cend1 has been implicated in coordination of cell cycle exit and differentiation of neuronal precursors. To further elucidate its function we generated Cend1 knock-out mice and analyzed their phenotype during postnatal cerebellar development. Cend1(-/-) mice showed no overt abnormalities in the gross anatomy of the cerebellum or other brain regions. However, detailed analysis revealed alterations in cerebellar layering arising from increased proliferation of granule cell precursors, delayed radial granule cell migration and impaired Purkinje cell differentiation. Accordingly, expression of Patched1, cyclin D1, reelin and brain-derived neurotrophic factor, which correlate with morphological development of the cerebellum, was altered in Cend1(-/-) mice. The observed anatomical and molecular alterations were accompanied by deficits in motor behaviour. Our results suggest that Cend1 is required for normal cerebellar development.
在神经系统发育过程中，神经祖细胞在增殖区产生，然后退出细胞周期并在远离这些区域的过程中分化。神经元蛋白 BM88/Cend1 被认为在协调细胞周期退出和神经元前体细胞的分化中起作用。为了进一步阐明其功能，我们生成了 Cend1 敲除小鼠，并在出生后小脑发育过程中分析了它们的表型。Cend1(-/-) 小鼠在小脑或其他脑区的大体解剖结构上没有明显异常。然而，详细分析显示，由于颗粒细胞前体细胞增殖增加、放射状颗粒细胞迁移延迟和浦肯野细胞分化受损，小脑分层发生改变。因此，与小脑形态发育相关的 Patched1、细胞周期蛋白 D1、reelin 和脑源性神经营养因子的表达在 Cend1(-/-) 小鼠中发生改变。观察到的解剖和分子改变伴随着运动行为缺陷。我们的结果表明 Cend1 是正常小脑发育所必需的。
