Choe Youngshik, Pleasure Samuel J, Mira Helena
Department of Neurology, Programs in Neuroscience, Developmental and Stem Cell Biology, UCSF Institute for Regeneration Medicine, San Francisco, California 94158.
Chronic Disease Programme, UFIEC, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid, Spain.
Cold Spring Harb Perspect Biol. 2015 Dec 4;8(3):a018887. doi: 10.1101/cshperspect.a018887.
Adult neurogenesis is dynamically regulated by a tangled web of local signals emanating from the neural stem cell (NSC) microenvironment. Both soluble and membrane-bound niche factors have been identified as determinants of adult neurogenesis, including morphogens. Here, we review our current understanding of the role and mechanisms of short-range morphogen ligands from the Wnt, Notch, Sonic hedgehog, and bone morphogenetic protein (BMP) families in the regulation of adult neurogenesis. These morphogens are ideally suited to fine-tune stem-cell behavior, progenitor expansion, and differentiation, thereby influencing all stages of the neurogenesis process. We discuss cross talk between their signaling pathways and highlight findings of embryonic development that provide a relevant context for understanding neurogenesis in the adult brain. We also review emerging examples showing that the web of morphogens is in fact tightly linked to the regulation of neurogenesis by diverse physiologic processes.
成体神经发生受到源自神经干细胞(NSC)微环境的错综复杂的局部信号网络的动态调控。可溶性和膜结合的生态位因子均已被确定为成体神经发生的决定因素,包括形态发生素。在此,我们综述了目前对来自Wnt、Notch、音猬因子和骨形态发生蛋白(BMP)家族的短程形态发生素配体在成体神经发生调控中的作用和机制的理解。这些形态发生素非常适合微调干细胞行为、祖细胞扩增和分化,从而影响神经发生过程的各个阶段。我们讨论了它们信号通路之间的相互作用,并强调了胚胎发育的研究结果,这些结果为理解成体大脑中的神经发生提供了相关背景。我们还综述了一些新出现的例子,这些例子表明形态发生素网络实际上与多种生理过程对神经发生的调控紧密相连。