Retinal fate and ganglion cell differentiation are potentiated by acidic FGF in an in vitro assay of early retinal development.
Retinal fate and ganglion cell differentiation are potentiated by acidic FGF in an in vitro assay of early retinal development.
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发表时间：
1992-03
期刊：
影响因子：
4.6
通讯作者：
François Guillemot;Constance L. Cepko
中科院分区：
文献类型：
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作者：
François Guillemot;Constance L. Cepko
脊椎动物眼睛发育的最早期事件之一是色素上皮和神经视网膜的建立。这些根本不同的组织来自内陷的视泡或视杯。即使在达到相当高级的分化状态之后，色素上皮也表现出与视杯相同的潜力，因为它可以“转分化”成神经视网膜。C. M.帕克和M。J. Hollenberg（Dev. 134，201-205，1989）发现，施用碱性成纤维细胞生长因子，结合视网膜去除，可以在体内引发这种转化。我们已经开发了一种定量的体外测定来研究成纤维细胞生长因子（FGF）家族在这种现象中的作用，并且更普遍地在早期视网膜发育中的作用。我们发现，该过程的几个方面，包括抑制色素上皮细胞分化，增殖和转化为视网膜的命运，并不严格相关。发现酸性和碱性FGF都增强该过程的所有方面，酸性FGF抑制色素沉着和诱导视网膜抗原的效力是碱性FGF的4至20倍。根据其浓度，酸性FGF诱导外植体中40%至80%的细胞产生通常由视网膜神经节细胞表达的抗原，视网膜神经节细胞是视网膜发育中产生的第一种细胞类型。这种神经节细胞标志物的表达可以在非分裂细胞以及分裂细胞中直接刺激，表明从色素上皮细胞到视网膜命运的转化不需要细胞分裂。这些数据表明，酸性FGF，或相关分子，可能在建立视网膜的命运从视杯的功能。这种作用可能直接或间接介导的诱导视网膜神经节细胞之间的多能祖细胞的命运。
One of the earliest events in vertebrate eye development is the establishment of the pigmented epithelium and neural retina. These fundamentally different tissues derive from the invaginated optic vesicle, or optic cup. Even after achieving a fairly advanced state of differentiation, the pigmented epithelium exhibits the same potential as the optic cup in that it can "transdifferentiate" into neural retina. C. M. Park and M. J. Hollenberg (Dev. Biol. 134, 201-205, 1989) discovered that administration of basic fibroblast growth factor, coupled with retinal removal, could trigger this transformation in vivo. We have developed a quantitative in vitro assay to study the role(s) of the fibroblast growth factor (FGF) family in this phenomenon and more generally in early retinal development. We found that several aspects of the process, including inhibition of pigmented epithelium differentiation, proliferation, and conversion to a retinal fate, were not strictly correlated. Both acidic and basic FGFs were found to potentiate all aspects of the process, with acidic FGF being 4 to 20 times more potent than basic FGF for inhibition of pigmentation and induction of retinal antigens. Depending upon its concentration, acidic FGF induced from 40% to 80% of the cells in the explants to produce antigens normally expressed by retinal ganglion cells, the first cell type to be generated in retinal development. Expression of such a ganglion cell marker could be directly stimulated in non-dividing cells as well as in dividing cells, indicating that conversion from the pigmented epithelial to retinal fate did not require cell division. These data suggest that acidic FGF, or a related molecule, may function in establishment of retinal fate from the optic cup. This effect may be directly or indirectly mediated by induction of retinal ganglion cell fate among multipotent progenitor cells.