identification of regulatory factors for generation of neurons by using live imaging of embryos

在大脑发育过程中，神经祖细胞（npc）增殖并产生有丝分裂后神经元。NPC扩张的程度和神经元产生的时间应该影响大脑的大小和形状。在这里，我们使用斑马鱼胚胎的视顶盖（OT）作为模型系统，表明npc的神经元生成不是一个随机事件，而是一个受空间和时间调控的过程，依赖于神经调节蛋白1型II (NRG1-II)，一种egf相关配体NRG1的同型异构体。下调NRG1-II或用ErbB抑制剂AG1478治疗可显著损害亚基底npc的神经元生成。去除AG1478恢复了基底下有丝分裂，但不影响顶室(V)区的有丝分裂。脑内注射可溶性人NRG1可改善NRG1- ii缺失胚胎的神经发生，这表明NRG1- erbb信号通路参与了发育中的脊椎动物脑内神经元的产生。

During brain development, neural progenitor cells (NPCs) proliferate and produce post-mitotic neurons. The extent of NPC expansion and the timing of neuron production should impact on the size and shape of the brain. Here, we show that neuronal generation from NPCs is not a stochastic event, but instead a spatially and temporally regulated process and depends on Neuregulin 1 type II (NRG1-II), an isoform of an EGF-related ligand NRG1, using the optic tectum (OT) of zebrafish embryos as a model system. Knocking-down NRG1-II or treatment with AG1478, an ErbB inhibitor, impaired neuron production from sub-basal NPCs prominently. The removal of AG1478 resumed sub-basal mitoses without affecting mitoses in the apical ventricular (V) region. Injection of soluble human NRG1 into the brain ameliorated neurogenesis of NRG1-II-depleted embryos, implying involvements of NRG1-ErbB signaling in neuron production in the developing vertebrate brain.