Division of Developmental Neurobiology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
Development. 2012 Aug;139(16):2978-87. doi: 10.1242/dev.080135. Epub 2012 Jul 4.
During central nervous system development, neural progenitors are patterned to form discrete neurogenic and non-neurogenic zones. In the zebrafish hindbrain, neurogenesis is organised by Fgf20a emanating from neurons located at each segment centre that inhibits neuronal differentiation in adjacent progenitors. Here, we have identified a molecular mechanism that clusters fgf20a-expressing neurons in segment centres and uncovered a requirement for this positioning in the regulation of neurogenesis. Disruption of hindbrain boundary cell formation alters the organisation of fgf20a-expressing neurons, consistent with a role of chemorepulsion from boundaries. The semaphorins Sema3fb and Sema3gb, which are expressed by boundary cells, and their receptor Nrp2a are required for clustering of fgf20a-expressing neurons at segment centres. The dispersal of fgf20a-expressing neurons that occurs following the disruption of boundaries or of Sema3fb/Sema3gb signalling leads to reduced FGF target gene expression in progenitors and an increased number of differentiating neurons. Sema3 signalling from boundaries thus links hindbrain segmentation to the positioning of fgf20a-expressing neurons that regulates neurogenesis.
在中枢神经系统发育过程中，神经祖细胞被模式化为形成离散的神经生成和非神经生成区。在斑马鱼后脑，神经发生由源自位于每个节段中心的神经元发出的 Fgf20a 组织，抑制相邻祖细胞中的神经元分化。在这里，我们已经确定了一种分子机制，该机制将表达 fgf20a 的神经元聚类在节段中心，并揭示了这种定位在神经发生调节中的必要性。破坏后脑边界细胞的形成会改变表达 fgf20a 的神经元的组织，这与边界的趋化排斥作用一致。边界细胞表达的 semaphorins Sema3fb 和 Sema3gb 及其受体 Nrp2a 对于 fgf20a 表达神经元在节段中心的聚类是必需的。边界破坏或 Sema3fb/Sema3gb 信号转导后表达 fgf20a 的神经元的分散导致祖细胞中 FGF 靶基因表达减少和分化神经元数量增加。因此，边界的 Sema3 信号从连接后脑分段到调节神经发生的 fgf20a 表达神经元的定位。
