命运决定子Numb在神经干/祖细胞不对称分裂及分化中的调控作用

Regulatory Mechanism of Numb in Asymmetric Cell Division and Differentiation of Neural Stem/Progenitor Cells

不对称分裂是干/祖细胞发育分化中的基本过程,膜相关蛋白Numb在其中发挥重要作用.Numb极性分布于细胞一侧,在干/祖细胞有丝分裂时不对等分配至两个子代细胞,使子代细胞产生不同分化命运.如一个保持在干/祖细胞状态,而另一个发育为神经元,这一过程主要通过抑制Notch信号通路发挥作用.近年在哺乳动物中的研究中发现,高强度Notch信号又能够反馈抑制Numb活性.Numb具有维持神经干/祖细胞增殖与促进分化的双重作用,Numb的命运决定作用还与Shh信号通路和p53蛋白等相关.另外,Numb参与调控细胞的粘连、迁移以及神经元轴突的分支与延长.本文主要对Numb在果蝇及哺乳动物神经干/祖细胞中的定位以及其在决定细胞命运和分化中的调控作用进行综述.

The asymmetric division is the basic process Numb plays an important role in regulation. Numb is of neural stem/progenitor cells development in which a membrane-associated protein that asymmetrically localizes and distributes during cell division of neural stem/progenitor cells. It turns the developmental fates of the daughter cells. One remains stem/progenitor cell and the other becomes neuron. Inhibition of Notch signaling is critical for the regulatory process. Recent studies in mammals have showed that high levels of Notch signaling can down-regulate Numb. Numb is required to promote neuronal differentiation as well as maintains neural stem/progenitor self-renewal. The regulation is related to Shh signaling and p53 protein. Meanwhile, Numb controls maintenance of cadherin-based adhesion, cell migration, axon arborization and extension as well. This paper reviewed the location and regulatory mechanism of Numb in determining cell fates and differentiation in neural stem/progenitor ceils of Drosophila and Mammals.