Program for Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
Curr Top Dev Biol. 2021;142:233-282. doi: 10.1016/bs.ctdb.2020.12.008. Epub 2021 Feb 17.
Neurons develop dendritic morphologies that bear cell type-specific features in dendritic field size and geometry, branch placement and density, and the types and distributions of synaptic contacts. Dendritic patterns influence the types and numbers of inputs a neuron receives, and the ways in which neural information is processed and transmitted in the circuitry. Even subtle alterations in dendritic structures can have profound consequences on neuronal function and are implicated in neurodevelopmental disorders. In this chapter, I review how growing dendrites acquire their exquisite patterns by drawing examples from diverse neuronal cell types in vertebrate and invertebrate model systems. Dendrite morphogenesis is shaped by intrinsic and extrinsic factors such as transcriptional regulators, guidance and adhesion molecules, neighboring cells and synaptic partners. I discuss molecular mechanisms that regulate dendrite morphogenesis with a focus on five aspects of dendrite patterning: (1) Dendritic cytoskeleton and cellular machineries that build the arbor; (2) Gene regulatory mechanisms; (3) Afferent cues that regulate dendritic arbor growth; (4) Space-filling strategies that optimize dendritic coverage; and (5) Molecular cues that specify dendrite wiring. Cell type-specific implementation of these patterning mechanisms produces the diversity of dendrite morphologies that wire the nervous system.
神经元发育出具有树突形态特征的树突,这些特征包括树突野大小和形状、分支位置和密度,以及突触接触的类型和分布。树突模式影响神经元接收的输入类型和数量,以及神经信息在电路中的处理和传递方式。即使树突结构的微小改变也会对神经元功能产生深远的影响,并与神经发育障碍有关。在本章中,我将通过来自脊椎动物和无脊椎动物模型系统中不同神经元细胞类型的例子,回顾生长中的树突如何通过自身获得其精细的模式。树突形态发生受内在和外在因素的影响,如转录调控因子、导向和黏附分子、相邻细胞和突触伙伴。我将讨论调节树突形态发生的分子机制,重点介绍树突模式形成的五个方面:(1)树突细胞骨架和构建树突的细胞机器;(2)基因调控机制;(3)调节树突分支生长的传入线索;(4)优化树突覆盖的空间填充策略;以及(5)指定树突布线的分子线索。这些模式形成机制的细胞类型特异性实施产生了连接神经系统的各种树突形态。