Signaling and transcriptional regulation in early mammalian eye development: a link between FGF and MITF.
Signaling and transcriptional regulation in early mammalian eye development: a link between FGF and MITF.
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发表时间：
2000-08
期刊：
影响因子：
4.6
通讯作者：
Minh-Thanh T. Nguyen;H. Arnheiter
中科院分区：
文献类型：
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作者：
Minh-Thanh T. Nguyen;H. Arnheiter
在脊椎动物眼睛发育过程中，视泡在其远侧尖端被划分为一个域，该域将产生神经视网膜，而在其近侧基部的另一个域将产生色素上皮。这两个域最初是双电位的，每个域都能够产生神经视网膜或色素上皮。这种分配依赖于外源性信号，特别是成纤维细胞生长因子，它们来自上覆的表面外胚层，并诱导相邻的神经上皮细胞承担神经视网膜的命运。使用小鼠视泡的外植体培养，我们证明，视神经上皮的bipotentiality与基本螺旋环螺旋拉链转录因子MITF，这是后来需要的唯一的色素上皮细胞的初始共表达，和一组不同的转录因子，成为限制到neuroretina。将成纤维细胞生长因子包被的珠粒植入接近视泡的基部导致MITF的快速下调和上皮的发育，所述上皮通过形态学、基因表达和缺乏色素沉着而类似于未来的神经视网膜。相反，去除表面外胚层导致远端视神经上皮中MITF的维持，缺乏神经视网膜特异性CHX10转录因子的表达，并将该上皮转化为色素单层。这种现象可以通过单独应用成纤维细胞生长因子来防止。在Mitf突变胚胎中，部分未来的色素上皮变厚，失去一些色素上皮转录因子的表达，获得神经视网膜转录因子的表达，并最终转分化成分层的第二视网膜。结果支持这样的观点，即双电位视神经上皮的特点是重叠的基因表达模式和选择性基因抑制，所带来的本地外部信号，导致分离成离散的表达域，因此，域规范。
During vertebrate eye development, the optic vesicle is partitioned into a domain at its distal tip that will give rise to the neuroretina, and another at its proximal base that will give rise to the pigmented epithelium. Both domains are initially bipotential, each capable of giving rise to either neuroretina or pigmented epithelium. The partitioning depends on extrinsic signals, notably fibroblast growth factors, which emanate from the overlying surface ectoderm and induce the adjacent neuroepithelium to assume the neuroretinal fate. Using explant cultures of mouse optic vesicles, we demonstrate that bipotentiality of the optic neuroepithelium is associated with the initial coexpression of the basic-helix-loop-helix-zipper transcription factor MITF, which is later needed solely in the pigmented epithelium, and a set of distinct transcription factors that become restricted to the neuroretina. Implantation of fibroblast growth factor-coated beads close to the base of the optic vesicle leads to a rapid downregulation of MITF and the development of an epithelium that, by morphology, gene expression, and lack of pigmentation, resembles the future neuroretina. Conversely, the removal of the surface ectoderm results in the maintenance of MITF in the distal optic epithelium, lack of expression of the neuroretinal-specific CHX10 transcription factor, and conversion of this epithelium into a pigmented monolayer. This phenomenon can be prevented by the application of fibroblast growth factor alone. In Mitf mutant embryos, parts of the future pigment epithelium become thickened, lose expression of a number of pigment epithelium transcription factors, gain expression of neuroretinal transcription factors, and eventually transdifferentiate into a laminated second retina. The results support the view that the bipotential optic neuroepithelium is characterized by overlapping gene expression patterns and that selective gene repression, brought about by local extrinsic signals, leads to the separation into discrete expression domains and, hence, to domain specification.