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

在脑发育过程中，神经前体细胞(NPC)增殖并产生有丝分裂后神经元。鼻咽癌扩大的程度和神经元产生的时机应该会影响大脑的大小和形状。在这里，我们以斑马鱼胚胎的视顶盖(OT)为模型系统，证明了神经前体细胞的神经元生成不是一个随机事件，而是一个空间和时间调节的过程，并且依赖于EGF相关配体NRG1的亚型NeuRegin 1 Type II(NRG1-II)。敲除NRG1-II或用ErbB抑制剂AG1478治疗，显著损害亚基础NPC的神经元产生。去除AG1478可恢复基础下有丝分裂，但不影响顶端脑室(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，暗示NRG1-ErbB信号参与发育中脊椎动物大脑中神经元的产生。

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.