A novel function for Hedgehog signalling in retinal pigment epithelium differentiation
A novel function for Hedgehog signalling in retinal pigment epithelium differentiation
复制标题
DOI：
10.1242/dev.00391
复制
发表时间：
2003-04-01
期刊：
影响因子：
4.6
通讯作者：
Harris, WA
中科院分区：
文献类型：
--
作者：
Perron, M;Boy, S;Harris, WA
音速刺猬参与眼场分离沿着近远轴。我们发现，Hh信号仍然是重要的定义方面的proximodistal轴视泡和视杯成熟。我们发现，其他两个刺猬蛋白，带状刺猬和头刺猬，有关的小鼠印度刺猬和沙漠刺猬，分别强烈表达在中央视网膜色素上皮细胞，但不包括周边色素上皮周围的睫状边缘区。相比之下，刺猬信号通路的下游组分Gli 2、Gli 3和X-Smoothened在该狭窄的外周上皮中表达。我们发现这个区域包含处于增殖状态的细胞。成年哺乳动物眼睛中的这个等效区域，即色素睫状上皮，已被鉴定为视网膜干细胞所在的区域。这些数据，结合双标记和其他视网膜色素上皮标记物的使用，表明蝌蚪胚胎的视网膜色素上皮细胞具有分子上不同的外周到中心轴。此外，Gli 2、Gli 3和X-Smoothened也在神经视网膜中表达，在睫状边缘区的最外围区域，在非洲爪蟾中发现视网膜干细胞，这表明它们是视网膜干细胞的良好标记物。为了测试Hedgehog通路在视网膜发生不同阶段的作用，我们通过注射显性负性形式的PKA或通过用环巴胺处理胚胎来阻断它来激活该通路。在早期阶段注射或处理的胚胎在视网膜中显示出明显的近远侧缺陷。有趣的是，在晚期阶段用环巴胺处理的胚胎的主要表型是RPE分化的严重缺陷。因此，这项研究提供了新的见解刺猬信号在形成的proximodistal轴的眼睛和视网膜色素上皮细胞的分化的作用。
Sonic hedgehog is involved in eye field separation along the proximodistal axis. We show that Hh signalling continues to be important in defining aspects of the proximodistal axis as the optic vesicle and optic cup mature. We show that two other Hedgehog proteins, Banded hedgehog and Cephalic hedgehog, related to the mouse Indian hedgehog and Desert hedgehog, respectively, are strongly expressed in the central retinal pigment epithelium but excluded from the peripheral pigment epithelium surrounding the ciliary marginal zone. By contrast, downstream components of the Hedgehog signalling pathway, Gli2, Gli3 and X-Smoothened, are expressed in this narrow peripheral epithelium. We show that this zone contains cells that are in the proliferative state. This equivalent region in the adult mammalian eye, the pigmented ciliary epithelium, has been identified as a zone in which retinal stem cells reside. These data, combined with double labelling and the use of other retinal pigment epithelium markers, show that the retinal pigment epithelium of tadpole embryos has a molecularly distinct peripheral to central axis. In addition, Gli2, Gli3 and X-Smoothened are also expressed in the neural retina, in the most peripheral region of the ciliary marginal zone, where retinal stem cells are found in Xenopus, suggesting that they are good markers for retinal stem cells. To test the role of the Hedgehog pathway at different stages of retinogenesis, we activated the pathway by injecting a dominant-negative form of PKA or blocking it by treating embryos with cyclopamine. Embryos injected or treated at early stages display clear proximodistal defects in the retina. Interestingly, the main phenotype of embryos treated with cyclopamine at late stages is a severe defect in RPE differentiation. This study thus provides new insights into the role of Hedgehog signalling in the formation of the proximodistal axis of the eye and the differentiation of retinal pigment epithelium.