Liu Qin, Londraville Richard, Marrs James A, Wilson Amy L, Mbimba Thomas, Murakami Tohru, Kubota Fumitaka, Zheng Weiping, Fatkins David G
Department of Biology, University of Akron, Akron, OH 44325, USA.
Dev Neurobiol. 2008 Jul;68(8):1107-22. doi: 10.1002/dneu.20646.
Cadherin cell-adhesion molecules play crucial roles in vertebrate development including the development of the visual system. Most studies have focused on examining functions of classical type I cadherins (e.g., cadherin-2) in visual system development. There is little information on the function of classical type II cadherins (e.g., cadherin-6) in the development of the vertebrate visual system. To gain insight into cadherin-6 role in the formation of the retina, we analyzed differentiation of retinal ganglion cells (RGCs), amacrine cells, and photoreceptors in zebrafish embryos injected with cadherin-6 specific antisense morpholino oligonucleotides. Differentiation of the retinal neurons in cadherin-6 knockdown embryos (cdh6 morphants) was analyzed using multiple markers. We found that expression of transcription factors important for retinal development was greatly reduced, and expression of Notch-Delta genes and proneural gene ath5 was altered in the cdh6 morphant retina. The retinal lamination was present in the morphants, although the morphant eyes were significantly smaller than control embryos due mainly to decreased cell proliferation. Differentiation of the RGCs, amacrine cells, and photoreceptors was severely disrupted in the cdh6 morphants due to a significant delay in neural differentiation. Our results suggest that cadherin-6 plays an important role in the normal formation of the zebrafish retina. (c) 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008.
钙黏蛋白细胞黏附分子在脊椎动物发育过程中发挥着关键作用,包括视觉系统的发育。大多数研究集中于考察经典I型钙黏蛋白(如钙黏蛋白-2)在视觉系统发育中的功能。关于经典II型钙黏蛋白(如钙黏蛋白-6)在脊椎动物视觉系统发育中的功能,所知甚少。为深入了解钙黏蛋白-6在视网膜形成中的作用,我们分析了注射钙黏蛋白-6特异性反义吗啉代寡核苷酸的斑马鱼胚胎中视网膜神经节细胞(RGCs)、无长突细胞和光感受器的分化情况。使用多种标记物分析了钙黏蛋白-6敲低胚胎(cdh6突变体)中视网膜神经元的分化。我们发现,对视网膜发育重要的转录因子表达大幅降低,且Notch-Delta基因和神经前体基因ath5的表达在cdh6突变体视网膜中发生改变。尽管突变体眼睛明显小于对照胚胎,主要是由于细胞增殖减少,但视网膜分层仍存在于突变体中。由于神经分化显著延迟,cdh6突变体中RGCs、无长突细胞和光感受器的分化受到严重破坏。我们的结果表明,钙黏蛋白-6在斑马鱼视网膜的正常形成中发挥重要作用。(c) 2008威利期刊公司。《发育神经生物学》,2008年。