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<p>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 <i>Egfr</i> 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 <i>Egfr</i> disrupts the <i>Egfr-pERK-Epb41l2</i> signaling axis, which in turn prevents glial progenitor cells from migrating outward. More importantly, <i>Egfr</i> deficiency during the critical period compromises astrocyte-neuron communication via the <i>Sema6a-Plxna2/4</i> ligand-receptor pair. This impaired intercellular crosstalk reduces neuronal dendritic complexity and excitability, ultimately culminating in depressive-like behaviors in adult mice.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月18日

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  • Xin Jiang,
  • Yanqing Qi,
  • Lin Yang,
  • Feihong Yang,
  • Rongliang Guo,
  • Liang Li,
  • Kun Wang,
  • Lichen Sun,
  • Dan Dai,
  • Hanchen Liu,
  • Yanjing Gao,
  • Mengge Sun,
  • Xiaolei Song,
  • Zhuangzhi Zhang,
  • Zhejun Xu,
  • Bin Luo,
  • Yunli Xie,
  • Zhengang Yang,
  • Miao He,
  • Dashi Qi,
  • Xiaodan Zhang,
  • Guoping Liu

摘要

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.