星形胶质细胞
神经油
神经科学
缝隙连接
生物
细胞生物学
中枢神经系统
细胞内
作者
Katherine T. Baldwin,Christabel Xin Tan,Samuel Strader,Changyu Jiang,Justin T Savage,Xabier Elorza‐Vidal,Ximena Contreras,Thomas Rülicke,Simon Hippenmeyer,Raúl Estévez,Ru-Rong Ji,Çağla Eroğlu
出处
期刊:Neuron
[Elsevier]
日期:2021-08-01
卷期号:109 (15): 2427-2442.e10
被引量:52
标识
DOI:10.1016/j.neuron.2021.05.025
摘要
Astrocytes extensively infiltrate the neuropil to regulate critical aspects of synaptic development and function. This process is regulated by transcellular interactions between astrocytes and neurons via cell adhesion molecules. How astrocytes coordinate developmental processes among one another to parse out the synaptic neuropil and form non-overlapping territories is unknown. Here we identify a molecular mechanism regulating astrocyte-astrocyte interactions during development to coordinate astrocyte morphogenesis and gap junction coupling. We show that hepaCAM, a disease-linked, astrocyte-enriched cell adhesion molecule, regulates astrocyte competition for territory and morphological complexity in the developing mouse cortex. Furthermore, conditional deletion of Hepacam from developing astrocytes significantly impairs gap junction coupling between astrocytes and disrupts the balance between synaptic excitation and inhibition. Mutations in HEPACAM cause megalencephalic leukoencephalopathy with subcortical cysts in humans. Therefore, our findings suggest that disruption of astrocyte self-organization mechanisms could be an underlying cause of neural pathology.
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