Department of Ophthalmology, SUNY Upstate Medical University, Syracuse, NY 13210, United States; The Center for Vision Research and SUNY Eye Institute, Upstate Medical University, Syracuse, New York, 13210, United States.
Dev Biol. 2013 Dec 1;384(1):26-40. doi: 10.1016/j.ydbio.2013.09.028. Epub 2013 Oct 1.
Proliferation and differentiation are tightly controlled during neural development. In the embryonic neural plate, primary neurogenesis is driven by the proneural pathway. Here we report the characterization of Maturin, a novel, evolutionarily conserved protein that is required for normal primary neurogenesis. Maturin is detected throughout the early nervous system, yet it is most strongly expressed in differentiating neurons of the embryonic fish, frog and mouse nervous systems. Maturin expression can be induced by the proneural transcription factors Neurog2, Neurod1, and Ebf3. Maturin overexpression promotes neurogenesis, while loss-of-function inhibits the differentiation of neuronal progenitors, resulting in neural plate expansion. Maturin knockdown blocks the ability of Neurog2, Neurod1, and Ebf3 to drive ectopic neurogenesis. Maturin and Pak3, are both required for, and can synergize to promote differentiation of the primary neurons in vivo. Together, our results suggest that Maturin functions during primary neurogenesis and is required for the proneural pathway to regulate neural differentiation.
神经发育过程中增殖和分化受到严格控制。在胚胎神经板中,初级神经发生由神经前体细胞途径驱动。在这里,我们报告了 Maturin 的特征,这是一种新的、进化上保守的蛋白质,对于正常的初级神经发生是必需的。Maturin 在整个早期神经系统中都有检测到,但在胚胎鱼类、青蛙和小鼠神经系统中正在分化的神经元中表达最强。Maturin 的表达可以被神经前体细胞转录因子 Neurog2、Neurod1 和 Ebf3 诱导。Maturin 的过表达促进神经发生,而功能丧失则抑制神经元祖细胞的分化,导致神经板扩张。Maturin 敲低阻断了 Neurog2、Neurod1 和 Ebf3 驱动异位神经发生的能力。Maturin 和 Pak3 都需要,并能协同促进体内初级神经元的分化。总之,我们的结果表明 Maturin 在初级神经发生过程中发挥作用,是神经前体细胞途径调节神经分化所必需的。