Department of Neurosciences, Case Western Reserve University, Cleveland, OH, United States.
Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
Front Neural Circuits. 2023 Feb 21;17:1121049. doi: 10.3389/fncir.2023.1121049. eCollection 2023.
Phrenic Motor Column (PMC) neurons are a specialized subset of motor neurons (MNs) that provide the only motor innervation to the diaphragm muscle and are therefore essential for survival. Despite their critical role, the mechanisms that control phrenic MN development and function are not well understood. Here, we show that catenin-mediated cadherin adhesive function is required for multiple aspects of phrenic MN development. Deletion of β- and γ- from MN progenitors results in perinatal lethality and a severe reduction in phrenic MN bursting activity. In the absence of catenin signaling, phrenic MN topography is eroded, MN clustering is lost and phrenic axons and dendrites fail to grow appropriately. Despite the essential requirement for catenins in early phrenic MN development, they appear to be dispensable for phrenic MN maintenance, as catenin deletion from postmitotic MNs does not impact phrenic MN topography or function. Our data reveal a fundamental role for catenins in PMC development and suggest that distinct mechanisms are likely to control PMC maintenance.
膈肌运动神经元（Phrenic Motor Column [PMC] 神经元）是运动神经元（Motor Neurons [MNs]）的一个特殊子集，为膈肌提供唯一的运动神经支配，因此对生存至关重要。尽管它们具有关键作用，但控制膈肌运动神经元发育和功能的机制尚不清楚。在这里，我们表明，连接蛋白介导的钙黏着蛋白黏附功能对于膈肌运动神经元发育的多个方面都是必需的。从 MN 祖细胞中缺失β-和γ-导致围产期致死和膈肌运动神经元爆发活动严重减少。在没有连接蛋白信号的情况下，膈肌运动神经元的拓扑结构被侵蚀，MN 聚类丢失，膈肌轴突和树突不能正常生长。尽管连接蛋白在早期膈肌运动神经元发育中是必需的，但它们似乎对膈肌运动神经元的维持是可有可无的，因为从有丝分裂后 MN 中缺失连接蛋白并不影响膈肌运动神经元的拓扑结构或功能。我们的数据揭示了连接蛋白在 PMC 发育中的基本作用，并表明可能存在控制 PMC 维持的不同机制。
