关键词: Eye development Retina Reverse signaling Semaphorin Zebrafish

Mesh : Animals Zebrafish / metabolism embryology Semaphorins / metabolism genetics Retina / metabolism Zebrafish Proteins / metabolism genetics Protein Domains Signal Transduction Ependymoglial Cells / metabolism cytology

来  源:   DOI:10.1242/jcs.261469

Abstract:
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.
摘要:
Sema6A(Sema6A)是一种排斥性引导分子,在中枢神经系统中起着许多作用。心,和骨骼发育,以及癌症中的免疫系统反应和细胞信号。斑马鱼中Sema6A或其受体PlexinA2的丢失导致眼睛变小和不适当的视网膜图案。在这里,我们研究了Sema6A细胞内结构域在斑马鱼眼发育和解剖中的潜在作用,这些表型依赖于正向信号传导和依赖于反向信号传导。我们对全长Sema6A(Sema6A-FL)或缺少胞内结构域的Sema6A(Sema6A-ΔC)的斑马鱼Sema6A形态进行了救援实验。我们发现,眼睛大小和视网膜图案不需要细胞内结构域,然而,它是视网膜完整性所必需的,Müller胶质细胞的数量和末端脚强度,并防止视网膜细胞死亡。胞内结构域的这种新功能表明Sema6A反向信号在斑马鱼眼发育中的作用。
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