Fuhrmann S, Levine E M, Reh T A
Department of Biological Structure, Box 357420, University of Washington, Seattle, WA 98195, USA.
Development. 2000 Nov;127(21):4599-609. doi: 10.1242/dev.127.21.4599.
The vertebrate eye develops from the neuroepithelium of the ventral forebrain by the evagination and formation of the optic vesicle. Classical embryological studies have shown that the surrounding extraocular tissues - the surface ectoderm and extraocular mesenchyme - are necessary for normal eye growth and differentiation. We have used explant cultures of chick optic vesicles to study the regulation of retinal pigmented epithelium (RPE) patterning and differentiation during early eye development. Our results show that extraocular mesenchyme is required for the induction and maintenance of expression of the RPE-specific genes Mitf and Wnt13 and the melanosomal matrix protein MMP115. In the absence of extraocular tissues, RPE development did not occur. Replacement of the extraocular mesenchyme with cranial mesenchyme, but not lateral plate mesoderm, could rescue expression of the RPE-marker Mitf. In addition to activating expression of RPE-specific genes, the extraocular mesenchyme inhibits the expression of the neural retina-specific transcription factor Chx10 and downregulates the eye-specific transcription factors Pax6 and Optx2. The TGF(&bgr;) family member activin can substitute for the extraocular mesenchyme by promoting expression of the RPE-specific genes and downregulating expression of the neural retina-specific markers. These data indicate that extraocular mesenchyme, and possibly an activin-like signal, pattern the domains of the optic vesicle into RPE and neural retina.
脊椎动物的眼睛由腹侧前脑的神经上皮通过视泡的外翻和形成而发育。经典胚胎学研究表明，周围的眼外组织——表面外胚层和眼外间充质——对于眼睛的正常生长和分化是必需的。我们利用鸡视泡的外植体培养来研究早期眼睛发育过程中视网膜色素上皮（RPE）的模式形成和分化调控。我们的结果表明，眼外间充质是诱导和维持RPE特异性基因Mitf和Wnt13以及黑素体基质蛋白MMP115表达所必需的。在没有眼外组织的情况下，RPE发育不会发生。用颅间充质而非侧板中胚层替代眼外间充质，可以挽救RPE标记物Mitf的表达。除了激活RPE特异性基因的表达外，眼外间充质还抑制神经视网膜特异性转录因子Chx10的表达，并下调眼特异性转录因子Pax6和Optx2的表达。转化生长因子（TGF）（β）家族成员激活素可以通过促进RPE特异性基因的表达和下调神经视网膜特异性标记物的表达来替代眼外间充质。这些数据表明，眼外间充质，可能还有一种类似激活素的信号，将视泡区域模式化为RPE和神经视网膜。
