McFarlane S, Zuber M E, Holt C E
Department of Cell Biology and Anatomy, Neuroscience Research Group, HMRB Room 171, University of Calgary, Calgary, Alberta, Canada, T2N 4N1.
Development. 1998 Oct;125(20):3967-75. doi: 10.1242/dev.125.20.3967.
The mature vertebrate retina contains seven major cell types that develop from an apparently homogenous population of precursor cells. Clonal analyses have suggested that environmental influences play a major role in specifying retinal cell identity. Fibroblast growth factor-2 is present in the developing retina and regulates the survival, proliferation and differentiation of developing retinal cells in culture. Here we have tested whether fibroblast growth factor receptor signaling biases retinal cell fate decisions in vivo. Fibroblast growth factor receptors were inhibited in retinal precursors in Xenopus embryos by expressing a dominant negative form of the receptor, XFD. Dorsal animal blastomeres that give rise to the retina were injected with cDNA expression constructs for XFD and a control non-functional mutant receptor, D48, and the cell fates of transgene-expressing cells in the mature retina determined. Fibroblast growth factor receptor blockade results in almost a 50% loss of photoreceptors and amacrine cells, and a concurrent 3.5-fold increase in Müller glia, suggesting a shift towards a Müller cell fate in the absence of a fibroblast growth factor receptor signal. Inhibition of non-fibroblast-growth-factor-mediated receptor signaling with a third mutant receptor, HAVO, alters cell fate in an opposite manner. These results suggest that it is the balance of fibroblast growth factor and non-fibroblast growth factor ligand signals that influences retinal cell genesis.
成熟的脊椎动物视网膜包含七种主要细胞类型，它们由一群看似同质的前体细胞发育而来。克隆分析表明，环境影响在确定视网膜细胞身份方面起主要作用。成纤维细胞生长因子-2存在于发育中的视网膜中，并在培养中调节发育中视网膜细胞的存活、增殖和分化。在这里，我们测试了成纤维细胞生长因子受体信号传导是否在体内影响视网膜细胞命运的决定。通过表达受体的显性负性形式XFD，在非洲爪蟾胚胎的视网膜前体细胞中抑制成纤维细胞生长因子受体。将产生视网膜的背侧动物卵裂球注射XFD和对照无功能突变受体D48的cDNA表达构建体，并确定成熟视网膜中表达转基因细胞的细胞命运。成纤维细胞生长因子受体阻断导致近50%的光感受器和无长突细胞丢失，同时米勒胶质细胞增加3.5倍，这表明在没有成纤维细胞生长因子受体信号的情况下，细胞命运向米勒细胞转变。用第三种突变受体HAVO抑制非成纤维细胞生长因子介导的受体信号传导，会以相反的方式改变细胞命运。这些结果表明，影响视网膜细胞发生的是成纤维细胞生长因子和非成纤维细胞生长因子配体信号的平衡。
