Investigaion of a new mechanism of growth factor signaling for regulation of neurogenesis

大脑发育始于脑室(V)区神经干细胞/放射状胶质细胞(NS/RG)的神经发生。RG细胞不仅能在V区自我更新，还能在脑室下区产生神经前体细胞(NP细胞)，NP细胞也能自我更新和/或产生有丝分裂后神经元。然而，对于NP细胞分化成神经元的调控机制却知之甚少。在这里，我们以斑马鱼胚胎的视顶盖(OT)为模型系统，证明了NP细胞分化成神经元是一个时空调控的过程，并且依赖于神经调节蛋白1(NRG1)。NRG1调控SV区NP细胞的细胞分裂。用重组人NRG1挽救NRG1缺失的胚胎表明，NRG1作为神经元产生的外部信号具有保守的作用。此外，活体成像显示，从胚胎中移除ErbB抑制剂会触发SV区NP细胞的神经元生成分裂。

Brain development starts with neurogenesis from neural stem/radial glial (NS/RG) cells in the ventricular (V) region. RG cells not only self-renew in the V region, but also give rise to neural progenitor (NP) cells, which also self-renew and/or produce post-mitotic neurons in the subventricular (SV) region. However, little is known about regulatory mechanisms for the generation of neurons from NP cells.Here, we showed that neuronal generation from NP cells is a spatially and temporally regulated process and depends on Neuregulin 1 (NRG1) using the optic tectum (OT) of zebrafish embryos as a model system. NRG1 regulates cell divisions of NP cells in the SV region. Rescue of NRG1-depleted embryos with recombinant human NRG1 suggested a conserved role for NRG1 as an extrinsic signal for neuron production. Moreover, live imaging showed that a removal of the ErbB inhibitor from embryos triggered neuron-generating divisions of NP cells in the SV region.