Delayed astrocyte development impairs Sema6a-Plxna2/4-mediated astrocyte-neuron crosstalk and causes depressive-like behavior

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.

Authors

Institutions

Publication Details

Journal
Nature Communications
Published
2026-07-18
DOI
https://doi.org/10.1038/s41467-026-75697-z
Primary Topic
Neurogenesis and neuroplasticity mechanisms
Type
article
Field-Weighted Citation Impact
0.00

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Delayed astrocyte development impairs Sema6a-Plxna2/4-mediated astrocyte-neuron crosstalk and causes depressive-like behavior

Dan Dai, Mengge Sun, Zhejun Xu, Yanqing Qi et al.
Nature Communications
Neurogenesis and neuroplasticity mechanisms
article

Delayed astrocyte development impairs Sema6a-Plxna2/4-mediated astrocyte-neuron crosstalk and causes depressive-like behavior

Dan Dai, Mengge Sun, Zhejun Xu, Yanqing Qi, Zhengang Yang, Yunli Xie, Bin Luo, Xia Song, Zhuangzhi Zhang, Feihong Yang, Guoping Liu, Miao He, Hanchen Liu, Gao Y, Li Li, Dashi Qi, Sun L, L Yang, Kun Wang, Rongliang Guo, Xiaodan Zhang, Xin Jiang
article en

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.

Nature Communications
Hebei University of Engineering (CN), Fudan University (CN), Institute of Neurobiology and Molecular Medicine (IT), China Academy of Chinese Medical Sciences (CN), Obstetrics and Gynecology Hospital of Fudan University (CN), Huashan Hospital (CN), Yangpu Hospital of Tongji University (CN), Nanjing University (CN)
Natural Science Foundation of Shanghai, National Natural Science Foundation of China, Fudan University, National Natural Science Foundation of China-Yunnan Joint Fund
Openalex Percentile: Top 11%
Neurogenesis and neuroplasticity mechanisms
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.