MRC Centre for Developmental and Biomedical Genetics, University of Sheffield, Sheffield, S10 2TN, UK.
Development. 2011 May;138(10):1893-902. doi: 10.1242/dev.064204.
The size, composition and functioning of the spinal cord is likely to depend on appropriate numbers of progenitor and differentiated cells of a particular class, but little is known about how cell numbers are controlled in specific cell cohorts along the dorsoventral axis of the neural tube. Here, we show that FatJ cadherin, identified in a large-scale RNA interference (RNAi) screen of cadherin genes expressed in the neural tube, is localised to progenitors in intermediate regions of the neural tube. Loss of function of FatJ promotes an increase in dp4-vp1 progenitors and a concomitant increase in differentiated Lim1(+)/Lim2(+) neurons. Our studies reveal that FatJ mediates its action via the Hippo pathway mediator Yap1: loss of downstream Hippo components can rescue the defect caused by loss of FatJ. Together, our data demonstrate that RNAi screens are feasible in the chick embryonic neural tube, and show that FatJ acts through the Hippo pathway to regulate cell numbers in specific subsets of neural progenitor pools and their differentiated progeny.
脊髓的大小、组成和功能可能取决于特定类别祖细胞和分化细胞的适当数量，但对于如何在神经管的背腹轴上的特定细胞群中控制细胞数量知之甚少。在这里，我们发现 FatJ 钙粘蛋白在神经管中表达的大规模 RNA 干扰 (RNAi) 筛选的钙粘蛋白基因中被鉴定出来，定位于神经管中间区域的祖细胞中。FatJ 功能丧失会促进 dp4-vp1 祖细胞的增加，并伴随分化的 Lim1(+)/Lim2(+) 神经元的增加。我们的研究表明，FatJ 通过 Hippo 通路介体 Yap1 发挥其作用：下游 Hippo 成分的缺失可以挽救由 FatJ 缺失引起的缺陷。总之，我们的数据表明，RNAi 筛选在鸡胚胎神经管中是可行的，并表明 FatJ 通过 Hippo 通路调节特定神经祖细胞池及其分化后代中特定亚群的细胞数量。
