Numb与神经发育

Numb and Neural Development

不对称性细胞分裂是一个母细胞通过一次分裂,产生两个不同命运的子细胞的分裂方式,是单细胞生物向多细胞生物进化的关键一步。根据现有的证据推论,不称性细胞分裂是在器官发育过程中产生细胞多样化的一种基本方式。Numb是第一个被发现决定多细胞生物不对称细胞分裂的信号蛋白。在果蝇中,Numb通过促进Notch泛素化拮抗Notch信号通路,从而决定子细胞的命运,后来的研究表明Numb是细胞内吞调节蛋白,并用通过内吞参与调节神经细胞的粘附,轴突的生长及细胞迁移等过程;并且发现Numb与肿瘤抑制基因p53、泛素化蛋白HDM2形成三聚体抑制p53的泛素化,从而调节肿瘤的恶性程度。本文系统地分析了Numb发现的历史及后来在脊椎动物中的作用和机制,重点介绍了Numb在神经发育过程中的功能。

Asymmetric cell division is a process that one mother cell generates two daughter cells with distinct cell fates, which is a crucial step in evolution from single-cell organism to multi-cellular organism. Based on the current evidence, it is presumed that asymmetric cell division is one of fundamental means in generating cell type diversity during organogenesis. Numb is the first signaling molecules found to determine asymmetric cell division in multi-cellular organisms. Numb promotes the ubiquination of Notch to antagonize Notch signaling pathway in determining cell fates in Drosophila external sensory organ, subsequently found to function as endocytic protein participating in the regulation of neurite extension and cell migration. Recently it has been reported that Numb forms a trimer with p53 and HDM2 to prevent p53 from being ubiquinated to regulate the malignancy of tumor cell. In this article, we have comprehensively reviewed the discovery history of Numb and subsequent findings of Numb function in vertebrate system.