Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, United States.
Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, United States; Department of Ophthalmology, Visual, and Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI, United States.
Curr Top Dev Biol. 2022;148:115-137. doi: 10.1016/bs.ctdb.2021.12.006. Epub 2022 Feb 28.
Since their first description, the clustered protocadherins (cPcdhs) have sparked interest for their potential to generate diverse cell-surface recognition cues and their widespread expression in the nervous system. Through the use of mouse models, we have learned a great deal about the functions served by cPcdhs, and how their molecular diversity is regulated. cPcdhs are essential contributors to a host of processes during neural circuit formation, including neuronal survival, dendritic and axonal branching, self-avoidance and targeting, and synapse formation. Their expression is controlled by the interplay of epigenetic marks with proximal and distal elements involving high order DNA looping, regulating transcription factor binding. Here, we will review various mouse models targeting the cPcdh locus and how they have been instructive in uncovering the regulation and function of the cPcdhs.
自从首次描述以来,聚集原钙黏蛋白 (cPcdh) 因其产生多样化细胞表面识别线索的潜力及其在神经系统中的广泛表达而引起了人们的兴趣。通过使用小鼠模型,我们已经了解了 cPcdh 所发挥的功能,以及它们的分子多样性是如何被调控的。cPcdh 是神经回路形成过程中许多过程的重要贡献者,包括神经元存活、树突和轴突分支、自我回避和靶向以及突触形成。它们的表达受到表观遗传标记与涉及高级 DNA 环的近端和远端元件之间相互作用的调控,从而调节转录因子的结合。在这里,我们将回顾针对 cPcdh 基因座的各种小鼠模型,以及它们如何有助于揭示 cPcdh 的调控和功能。