Sommer Lukas, Rao Mahendra
Institute of Cell Biology, Swiss Federal Institute of Technology, ETH-Hoenggerberg HPM E38, CH-8093 Zürich, Switzerland.
Prog Neurobiol. 2002 Jan;66(1):1-18. doi: 10.1016/s0301-0082(01)00022-3.
Normal CNS development involves the sequential differentiation of multipotent stem cells. Alteration of the numbers of stem cells, their self-renewal ability, or their proliferative capacity will have major effects on the appropriate development of the nervous system. In this review, we discuss different mechanisms that regulate neural stem cell differentiation. Proliferation signals and cell cycle regulators may regulate cell kinetics or total number of cell divisions. Loss of trophic support and cytokine receptor activation may differentially contribute to the induction of cell death at specific stages of development. Signaling from differentiated progeny or asymmetric distribution of specific molecules may alter the self-renewal characteristics of stem cells. We conclude that the final decision of a cell to self-renew, differentiate or remain quiescent is dependent on an integration of multiple signaling pathways and at each instant will depend on cell density, metabolic state, ligand availability, type and levels of receptor expression, and downstream cross-talk between distinct signaling pathways.
正常的中枢神经系统发育涉及多能干细胞的顺序分化。干细胞数量、自我更新能力或增殖能力的改变将对神经系统的正常发育产生重大影响。在本综述中，我们讨论调节神经干细胞分化的不同机制。增殖信号和细胞周期调节因子可能调节细胞动力学或细胞分裂总数。营养支持的丧失和细胞因子受体激活可能在发育的特定阶段对细胞死亡的诱导有不同的作用。来自分化后代的信号或特定分子的不对称分布可能改变干细胞的自我更新特性。我们得出结论，细胞自我更新、分化或保持静止的最终决定取决于多种信号通路的整合，并且在每个时刻都将取决于细胞密度、代谢状态、配体可用性、受体表达的类型和水平，以及不同信号通路之间的下游相互作用。
