Vagnozzi Alicia N, Moore Matthew T, de Boer Raquel López, Agarwal Aambar, Zampieri Niccolò, Landmesser Lynn T, Philippidou Polyxeni
Department of Neurosciences, Case Western Reserve University, Cleveland, OH, USA.
Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
bioRxiv. 2023 Jan 19:2023.01.18.524559. doi: 10.1101/2023.01.18.524559.
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 - and -catenin 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.
膈运动柱（PMC）神经元是运动神经元（MNs）的一个特殊子集，它们为膈肌提供唯一的运动神经支配，因此对生存至关重要。尽管它们起着关键作用，但控制膈运动神经元发育和功能的机制尚未完全了解。在这里，我们表明连环蛋白介导的钙黏蛋白黏附功能是膈运动神经元发育多个方面所必需的。从运动神经元祖细胞中删除β-连环蛋白和α-连环蛋白会导致围产期死亡，并使膈运动神经元的爆发活动严重减少。在没有连环蛋白信号的情况下，膈运动神经元的拓扑结构受到破坏，运动神经元聚集消失，膈运动神经元的轴突和树突无法正常生长。尽管连环蛋白在早期膈运动神经元发育中是必不可少的，但它们似乎对膈运动神经元的维持是可有可无的，因为从有丝分裂后运动神经元中删除连环蛋白不会影响膈运动神经元的拓扑结构或功能。我们的数据揭示了连环蛋白在PMC发育中的基本作用，并表明不同的机制可能控制PMC的维持。
