Wang Miaoxing, Han Xujun, Lee Yunfei, Takayama Rie, Sato Makoto
Mathematical Neuroscience Unit, Institute for Frontier Science Initiative, Kanazawa University, Kanazawa, Ishikawa, Japan.
Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
Sci Adv. 2025 Aug 15;11(33):eadv7490. doi: 10.1126/sciadv.adv7490. Epub 2025 Aug 13.
Columns are the morphological and functional units containing multiple neurons in the brain. The molecular mechanisms of column formation are largely unknown. Ephrin/Eph signaling mediates a variety of developmental processes. Ephrin acts as a ligand for Eph to regulate forward signaling, whereas Eph acts as a ligand for Ephrin to regulate reverse signaling. However, whether and how the uni- or bidirectional Ephrin/Eph signaling is involved in column formation remains elusive. In this study, we show that Ephrin and Eph regulate the morphology and location of columnar neurons through bidirectional repulsive signaling. Furthermore, Eph ligand triggers cytoplasmic tyrosine phosphorylation of Ephrin under the control of Src kinases and Fasciclin 2 (Fas2), forming the Ephrin/Src/Fas2 complex to promote reverse signaling through a downstream regulator, Rac1. This study provides the detailed analysis of the molecular interactions involved in column formation using the fly brain as a model.
柱是大脑中包含多个神经元的形态和功能单位。柱形成的分子机制在很大程度上尚不清楚。 Ephrin/Eph信号传导介导多种发育过程。 Ephrin作为Eph的配体来调节正向信号传导，而Eph作为Ephrin的配体来调节反向信号传导。然而，单向或双向的Ephrin/Eph信号传导是否以及如何参与柱形成仍然不清楚。在本研究中，我们表明Ephrin和Eph通过双向排斥信号传导调节柱状神经元的形态和位置。此外，Eph配体在Src激酶和Fasciclin 2（Fas2）的控制下触发Ephrin的细胞质酪氨酸磷酸化，形成Ephrin/Src/Fas2复合物，通过下游调节因子Rac1促进反向信号传导。本研究以果蝇大脑为模型，对参与柱形成的分子相互作用进行了详细分析。
