Abstract
To understand how the nervous system develops from a small pool of progenitors during early embryonic development,it is fundamentally important to identify the diversity of neuronal subtypes,decode the origin of neuronal diversity,and uncover the principles governing neuronal specification across different regions.Recent single-cell analyses have systematically identified neuronal diversity at unprecedented scale and speed,leaving the deconstruc-tion of spatiotemporal mechanisms for generating neuronal diversity an imperative and paramount challenge.In this review,we highlight three distinct strategies deployed by neural progenitors to produce diverse neuronal subtypes,including predetermined,stochastic,and cascade diversify-ing models,and elaborate how these strategies are imple-mented in distinct regions such as the neocortex,spinal cord,retina,and hypothalamus.Importantly,the identity of neural progenitors is defined by their spatial position and temporal patterning factors,and each type of progenitor cell gives rise to distinguishable cohorts of neuronal sub-types.Microenvironmental cues,spontaneous activity,and connectional pattern further reshape and diversify the fate of unspecialized neurons in particular regions.The illumination of how neuronal diversity is generated will pave the way for producing specific brain organoids to model human disease and desired neuronal subtypes for cell therapy,as well as understanding the organization of functional neural circuits and the evolution of the nervous system.
基金项目
National Key R&D Program of China(2019YFA0801900)
National Key R&D Program of China(2018YFA0801104)
National Natural Science Foundation of China(81891002)
National Natural Science Foundation of China(32070972)
National Natural Science Foundation of China(31921002)
National Natural Science Foundation of China(31771131)
Strategic Priority Research Program of Chinese Academy of Sciences(XDB32020000)
Hundred-Talent Program(Chinese Academy of Sciences)()
Beijing Municipal Science & Technology Commission(Z210010)
Beijing Municipal Science & Technology Commission(Z181100001518001)
维普
万方数据