Delayed astrocyte development impairs Sema6a-Plxna2/4-mediated astrocyte-neuron crosstalk and causes depressive-like behavior
Abstract
Abstract Neural functions and circuit formation rely on intricate crosstalk among various cell types during critical periods. Disruptions or delays in this crosstalk between neurons and astrocytes lead to abnormal neural functions and neurodevelopmental disorders. However, the lack of robust mouse models to study the crosstalk between astrocytes and neurons thus renders unclear the implications of impeding such interactions. In this study, we demonstrate that Egfr knockout during the critical period of neuronal maturation results in a transient absence of astrocytes, with recovery observed in adult mice. This model thus provides a unique opportunity to investigate the effects of impaired astrocyte-neuron communication during development. Mechanically, we show that loss of Egfr disrupts the Egfr-pERK-Epb41l2 signaling axis, which in turn prevents glial progenitor cells from migrating outward. More importantly, Egfr deficiency during the critical period compromises astrocyte-neuron communication via the Sema6a-Plxna2/4 ligand-receptor pair. This impaired intercellular crosstalk reduces neuronal dendritic complexity and excitability, ultimately culminating in depressive-like behaviors in adult mice.
Article Details
Authors (22)
Xin Jiang
Yanqing Qi
Lin Yang
Feihong Yang
Department of Neurology, Zhongshan Hospital, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain Science, Fudan University
Rongliang Guo
Department of Central Laboratory, Affiliated Hospital of Hebei University of Engineering, Handan
Liang Li
Kun Wang
Beijing National Laboratory for Molecular Science, State Key Laboratory of Rare Earth Materials Chemistry and Applications, College of Chemistry and Molecular Engineering
Lichen Sun
Dan Dai
Hanchen Liu
Yanjing Gao
State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University, Qianjin Street 2699, Changchun 130012, P. R. China
Mengge Sun
Department of Neurology, Zhongshan Hospital, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain Science, Fudan University
Xiaolei Song
Zhuangzhi Zhang
Department of Neurology, Zhongshan Hospital, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain Science, Fudan University
Zhejun Xu
Department of Neurology, Zhongshan Hospital, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain Science, Fudan University
Bin Luo
Australian Institute for Bioengineering and Nanotechnology
Yunli Xie
Department of Anesthesia, State Key Laboratory of Brain Function and Disorders and Ministry of Education Frontiers Center for Brain Science, Institutes of Brain Science, and Zhongshan Hospital, Fudan University
Zhengang Yang
Department of Neurology, Zhongshan Hospital, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain Science, Fudan University
Miao He
Dashi Qi
Center for Clinical Research and Translational Medicine, Yangpu Hospital, School of Medicine, Tongji University
Xiaodan Zhang
Institute of Photoelectronic Thin Film Devices and Technology, Renewable Energy Conversion and Storage Center, State Key Laboratory of Photovoltaic Materials and Cells
Guoping Liu
Department of Neurology, Zhongshan Hospital, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain Science, Fudan University