为了了解神经系统是如何在早期胚胎发育过程中从一小部分祖细胞中发展而来的,识别神经元亚型的多样性至关重要,解码神经元多样性的起源,并揭示控制不同区域神经元规范的原理。最近的单细胞分析以前所未有的规模和速度系统地识别了神经元多样性,使产生神经元多样性的时空机制的解构成为当务之急和最重要的挑战。在这次审查中,我们强调了神经祖细胞部署的三种不同的策略来产生不同的神经元亚型,包括预先确定的,随机,和级联多样化模型,并阐述这些策略是如何在不同的区域实施的,比如大脑皮层,脊髓,视网膜,还有下丘脑.重要的是,神经祖细胞的身份由它们的空间位置和时间模式因子定义,并且每种类型的祖细胞都会产生可区分的神经元亚型队列。微环境线索,自发活动,和连接模式进一步重塑和多样化非特化神经元在特定区域的命运。神经元多样性如何产生的照明将为产生特定的脑类器官铺平道路,以模拟人类疾病和细胞治疗所需的神经元亚型。以及理解功能性神经回路的组织和神经系统的进化。
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 deconstruction 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 diversifying models, and elaborate how these strategies are implemented 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 subtypes. 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.