Regulation of <i>Scn1b</i> and <i>Scn2a</i> by BCL9 in cortical neurodevelopment and neuronal excitability

作者：Yifang Kuang, Ying Zhou, Beimeng Yang, Abdul Aziz Khan, Ziying Wang, Dongni Ma, Xu Zhang, Yuting Li, Caiqin Li, Guang He, Eiki Takahashi, Sanbin Shen, Thaise Toutain, Daniel de Almeida-Filho, Paul W. Frankland, Zhaohui Lan, Weidong Li · 发表于：The Innovation Life · 年份：2026 · DOI：10.59717/j.xinn-life.2026.100213 · 研究领域：Wnt/β-catenin signaling in development and cancer、Ion channel regulation and function、Electroconvulsive Therapy Studies

<p>The convergence of oncology and neurodevelopmental research has uncovered compelling links between genetic factors and mental health. Among these, B-cell chronic lymphocytic leukemia/lymphoma 9 (<i>BCL9</i>), located on human chromosome 1q21.1, has been identified as a key oncogene in precursor B-cell acute lymphoblastic leukemia (B-ALL). Subsequent studies have established that <i>Bcl9</i> promotes tumorigenesis through activation of the Wnt/β-catenin signaling pathway. Emerging evidence from human genetic studies further implicates common variants of <i>Bcl9</i> in increased susceptibility to neurodevelopmental disorders, including schizophrenia and bipolar disorder. Despite growing interest in its role beyond cancer, the neurobiological functions of <i>Bcl9</i> remain poorly defined. In this study, we systematically investigated the role of <i>Bcl9</i> in neurodevelopment using mouse models. By employing in utero electroporation-mediated gene knockdown techniques and conditional knockout (cKO) mice, we demonstrate that <i>Bcl9</i> deficiency disrupts Wnt-dependent signal transduction and leads to upregulation of voltage-gated sodium channel (Nav) expression, thereby results in increased sodium current density but paradoxically reduced action potential firing. Based on our experimental findings, <i>Bcl9</i> and/or the <i>Bcl9</i> complexes may regulate the promoter regio...