Ossipova Olga, Ezan Jerome, Sokol Sergei Y
Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Dev Cell. 2009 Aug;17(2):222-33. doi: 10.1016/j.devcel.2009.06.010.
Generation of neurons in the vertebrate central nervous system requires a complex transcriptional regulatory network and signaling processes in polarized neuroepithelial progenitor cells. Here we demonstrate that neurogenesis in the Xenopus neural plate in vivo and mammalian neural progenitors in vitro involves intrinsic antagonistic activities of the polarity proteins PAR-1 and aPKC. Furthermore, we show that Mind bomb (Mib), a ubiquitin ligase that promotes Notch ligand trafficking and activity, is a crucial molecular substrate for PAR-1. The phosphorylation of Mib by PAR-1 results in Mib degradation, repression of Notch signaling, and stimulation of neuronal differentiation. These observations suggest a conserved mechanism for neuronal fate determination that might operate during asymmetric divisions of polarized neural progenitor cells.
脊椎动物中枢神经系统中神经元的生成需要极化神经上皮祖细胞中复杂的转录调控网络和信号传导过程。在这里，我们证明非洲爪蟾神经板中的体内神经发生以及哺乳动物神经祖细胞中的体外神经发生涉及极性蛋白PAR-1和非典型蛋白激酶C（aPKC）的内在拮抗活性。此外，我们表明促进Notch配体运输和活性的泛素连接酶Mind bomb（Mib）是PAR-1的关键分子底物。PAR-1对Mib的磷酸化导致Mib降解、Notch信号传导受抑制以及神经元分化受到刺激。这些观察结果提示了一种保守的神经元命运决定机制，该机制可能在极化神经祖细胞的不对称分裂过程中起作用。
