Catenin signaling controls phrenic motor neuron development and function during a narrow temporal window.

IF 3.4 3区 医学 Q2 NEUROSCIENCES
Frontiers in Neural Circuits Pub Date : 2023-02-21 eCollection Date: 2023-01-01 DOI:10.3389/fncir.2023.1121049
Alicia N Vagnozzi, Matthew T Moore, Raquel López de Boer, Aambar Agarwal, Niccolò Zampieri, Lynn T Landmesser, Polyxeni Philippidou
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Abstract

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-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.

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连环蛋白信号控制膈运动神经元的发育和功能在一个狭窄的时间窗口。
膈肌运动柱(PMC)神经元是运动神经元(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MN发育和功能的机制尚不清楚。在这里,我们发现连环蛋白介导的钙粘蛋白粘附功能是膈MN发展的多个方面所必需的。MN祖细胞中β-和γ-连环蛋白的缺失导致围产期死亡和膈MN爆发活性的严重降低。在缺乏连环蛋白信号传导的情况下,膈MN地形被侵蚀,MN聚集丧失,膈轴突和树突不能适当生长。尽管在早期膈MN发展中对连环蛋白有重要要求,但它们似乎对膈MN维持是可有可无的,因为有丝分裂后MN的连环蛋白缺失不会影响膈MN的地形或功能。我们的数据揭示了连环蛋白在PMC发展中的基本作用,并表明不同的机制可能控制PMC的维持。
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来源期刊
CiteScore
6.00
自引率
5.70%
发文量
135
审稿时长
4-8 weeks
期刊介绍: Frontiers in Neural Circuits publishes rigorously peer-reviewed research on the emergent properties of neural circuits - the elementary modules of the brain. Specialty Chief Editors Takao K. Hensch and Edward Ruthazer at Harvard University and McGill University respectively, are supported by an outstanding Editorial Board of international experts. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics and the public worldwide. Frontiers in Neural Circuits launched in 2011 with great success and remains a "central watering hole" for research in neural circuits, serving the community worldwide to share data, ideas and inspiration. Articles revealing the anatomy, physiology, development or function of any neural circuitry in any species (from sponges to humans) are welcome. Our common thread seeks the computational strategies used by different circuits to link their structure with function (perceptual, motor, or internal), the general rules by which they operate, and how their particular designs lead to the emergence of complex properties and behaviors. Submissions focused on synaptic, cellular and connectivity principles in neural microcircuits using multidisciplinary approaches, especially newer molecular, developmental and genetic tools, are encouraged. Studies with an evolutionary perspective to better understand how circuit design and capabilities evolved to produce progressively more complex properties and behaviors are especially welcome. The journal is further interested in research revealing how plasticity shapes the structural and functional architecture of neural circuits.
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