Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK.
Developmental Neurobiology Unit, Instituto de Biomedicina de Valencia IBV-CSIC, Valencia 46012, Spain.
Genetics. 2024 Oct 7;228(2). doi: 10.1093/genetics/iyae116.
Animals rely on their nervous systems to process sensory inputs, integrate these with internal signals, and produce behavioral outputs. This is enabled by the highly specialized morphologies and functions of neurons. Neuronal cells share multiple structural and physiological features, but they also come in a large diversity of types or classes that give the nervous system its broad range of functions and plasticity. This diversity, first recognized over a century ago, spurred classification efforts based on morphology, function, and molecular criteria. Caenorhabditis elegans, with its precisely mapped nervous system at the anatomical level, an extensive molecular description of most of its neurons, and its genetic amenability, has been a prime model for understanding how neurons develop and diversify at a mechanistic level. Here, we review the gene regulatory mechanisms driving neurogenesis and the diversification of neuron classes and subclasses in C. elegans. We discuss our current understanding of the specification of neuronal progenitors and their differentiation in terms of the transcription factors involved and ensuing changes in gene expression and chromatin landscape. The central theme that has emerged is that the identity of a neuron is defined by modules of gene batteries that are under control of parallel yet interconnected regulatory mechanisms. We focus on how, to achieve these terminal identities, cells integrate information along their developmental lineages. Moreover, we discuss how neurons are diversified postembryonically in a time-, genetic sex-, and activity-dependent manner. Finally, we discuss how the understanding of neuronal development can provide insights into the evolution of neuronal diversity.
动物依赖神经系统来处理感觉输入，将这些输入与内部信号整合，并产生行为输出。这是通过神经元高度专业化的形态和功能实现的。神经元细胞具有多种结构和生理特征，但它们也有多种类型或类别，这使得神经系统具有广泛的功能和可塑性。这种多样性早在一个多世纪前就被首次认识到，促使人们根据形态、功能和分子标准进行分类。秀丽隐杆线虫(Caenorhabditis elegans) 因其在解剖学水平上精确映射的神经系统、对其大多数神经元的广泛分子描述以及其遗传可操作性，一直是理解神经元如何在机制水平上发育和多样化的主要模型。在这里，我们回顾了驱动神经发生和神经元类和子类多样化的基因调控机制。我们讨论了我们目前对神经元前体细胞的特化及其分化的理解，包括涉及的转录因子以及随后的基因表达和染色质景观变化。出现的一个核心主题是，神经元的身份是由受平行但相互连接的调控机制控制的基因电池模块定义的。我们专注于细胞如何沿着其发育谱系整合信息，以实现这些终末身份。此外，我们还讨论了神经元如何在胚胎后以时间、遗传性别和活动依赖的方式多样化。最后，我们讨论了对神经元发育的理解如何为神经元多样性的进化提供见解。
