Coupling of cell migration with neurogenesis by proneural bHLH factors
Coupling of cell migration with neurogenesis by proneural bHLH factors
复制标题
DOI：
10.1073/pnas.0510419103
复制
发表时间：
2006-01-31
影响因子：
11.1
通讯作者：
Sun, YE
中科院分区：
文献类型：
--
作者：
Ge, WH;He, F;Sun, YE
细胞出生后，几乎所有哺乳动物中枢神经系统中的神经元都会迁移。目前尚不清楚细胞迁移是否以及如何与神经发生相结合。在这里，我们报告，前神经碱性螺旋-环-螺旋（bHLH）转录因子不仅启动神经元分化，但也增强细胞迁移。从机制上讲，前神经bHLH因子调节与迁移密切相关的基因的表达，包括RhoA小GTP酶的下调和doublecortin和p35的上调，这反过来又调节肌动蛋白和微管细胞骨架组装，使新产生的神经元迁移。此外，我们报告说，几个DNA结合缺陷的原神经基因，未能启动神经元分化仍然激活迁移，而不同的突变的原神经基因，导致启动细胞迁移失败，仍然导致强大的神经元分化。总的来说，这些数据表明，转录程序的神经发生和迁移的bHLH因子通过部分不同的机制进行调节。
After cell birth, almost all neurons in the mammalian central nervous system migrate. It is unclear whether and how cell migration is coupled with neurogenesis. Here we report that proneural basic helix-loop-helix (bHLH) transcription factors not only initiate neuronal differentiation but also potentiate cell migration. Mechanistically, proneural bHLH factors regulate the expression of genes critically involved in migration, including down-regulation of RhoA small GTPase and up-regulation of doublecortin and p35, which, in turn, modulate the actin and microtubule cytoskeleton assembly and enable newly generated neurons to migrate. In addition, we report that several DNA-binding-deficient proneural genes that fail to initiate neuronal differentiation still activate migration, whereas a different mutation of a proneural gene that causes a failure in initiating cell migration still leads to robust neuronal differentiation. Collectively, these data suggest that transcription programs for neurogenesis and migration are regulated by bHLH factors through partially distinct mechanisms.