Semaphorin6A (Sema6A) 是一种排斥性引导分子，在中枢神经系统、心脏和骨骼发育以及癌症中的免疫系统反应和细胞信号传导中发挥多种作用。斑马鱼中 Sema6A 或其受体 PlexinA2 的缺失会导致眼睛变小和视网膜图案不正确。在这里，我们研究了 Sema6A 胞内结构域在斑马鱼眼睛发育中的潜在作用，并剖析了哪些表型依赖于正向信号传导，哪些表型依赖于反向信号传导。我们对具有全长 Sema6A (Sema6A-FL) 或缺乏胞内结构域的 Sema6A (Sema6A-ΔC) 的斑马鱼 Sema6A 变形体进行了拯救实验。我们发现细胞内结构域对于眼睛大小和视网膜图案不是必需的，但对于视网膜完整性、米勒胶质细胞的数量和末端足强度以及防止视网膜细胞死亡是必需的。细胞内结构域的这一新功能表明 Sema6A 反向信号传导在斑马鱼眼睛发育中的作用。© 2024。由 The Company of Biologies Ltd 出版。

Semaphorin6A (Sema6A) is a repulsive guidance molecule that plays many roles in central nervous system, heart, and bone development, as well as immune system responses and cell signaling in cancer. Loss of Sema6A or its receptor PlexinA2 in zebrafish leads to smaller eyes and improper retinal patterning. Here we investigate a potential role for the Sema6A intracellular domain in zebrafish eye development and dissect which phenotypes rely on forward signaling and which rely on reverse signaling. We performed rescue experiments on zebrafish Sema6A morphants with either full-length Sema6A (Sema6A-FL) or Sema6A lacking its intracellular domain (Sema6A-ΔC). We identified that the intracellular domain is not required for eye size and retinal patterning, however it is required for retinal integrity, the number and end feet strength of Müller glia and protecting against retinal cell death. This novel function for the intracellular domain suggests a role for Sema6A reverse signaling in zebrafish eye development.© 2024. Published by The Company of Biologists Ltd.