Babb Sherry G, Kotradi Shannon M, Shah Bijal, Chiappini-Williamson Christin, Bell Lauren N, Schmeiser Glen, Chen Elbert, Liu Qin, Marrs James A
Department of Medicine, Indiana University Medical Center, Indianapolis, Indiana 56202-5130, USA.
Dev Dyn. 2005 Jul;233(3):930-45. doi: 10.1002/dvdy.20431.
In zebrafish, R-cadherin (cadherin-4 or Cdh4) is expressed in the retina and in retinorecipient brain regions, suggesting that Cdh4 functions during visual system development. Cdh4 function was examined during retinogenesis and retinal axon outgrowth using antisense morpholino oligonucleotides and mutant Cdh4 construct expression. In knockdowns, Cdh4 was reduced or absent, eyes were small, and retinae lacked discrete laminae. Increased cell death produced the small eye phenotype. Zn5-, Pax6-, and zpr-1-positive cells were reduced or absent in knockdown retinas but, when present, were in the correct laminae. Cdh4 knockdowns had sparse or absent retinal ganglion cell axons. When present, axons projected contralaterally but lacked fine branching and failed to reach the tectum or arborize the entire tectum. Mutant Cdh4 construct expression during retinal ganglion cell differentiation reduced or ablated neurite formation. Cdh4 is necessary for neural retina survival and differentiation, and required for normal retinotectal projection formation and tectal arborization.
在斑马鱼中，R-钙黏蛋白（钙黏蛋白-4或Cdh4）在视网膜和接受视网膜投射的脑区表达，这表明Cdh4在视觉系统发育过程中发挥作用。利用反义吗啉代寡核苷酸和突变型Cdh4构建体表达，在视网膜发生和视网膜轴突生长过程中检测了Cdh4的功能。在敲低实验中，Cdh4减少或缺失，眼睛变小，视网膜缺乏离散的板层。细胞死亡增加导致了小眼表型。在敲低的视网膜中，Zn5、Pax6和zpr-1阳性细胞减少或缺失，但如果存在，则位于正确的板层中。Cdh4敲低的视网膜神经节细胞轴突稀疏或缺失。当轴突存在时，它们向对侧投射，但缺乏精细分支，无法到达顶盖或在整个顶盖形成分支。在视网膜神经节细胞分化过程中，突变型Cdh4构建体的表达减少或消除了神经突的形成。Cdh4对神经视网膜的存活和分化是必需的，也是正常视网膜顶盖投射形成和顶盖分支所必需的。
