RPE specification in the chick is mediated by surface ectoderm-derived BMP and Wnt signalling
RPE specification in the chick is mediated by surface ectoderm-derived BMP and Wnt signalling
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DOI：
10.1242/dev.096990
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发表时间：
2013-12-15
期刊：
影响因子：
4.6
通讯作者：
Vogel-Hoepker, Astrid
中科院分区：
文献类型：
--
作者：
Steinfeld, Joerg;Steinfeld, Ichie;Vogel-Hoepker, Astrid
视网膜色素上皮（RPE）对于脊椎动物眼睛的发育和视力是不可或缺的。在视神经泡模式化的经典模型中，表面外胚层产生成纤维细胞生长因子（FGF），其指定远端神经视网膜（NR），而从近端间充质释放的TGFβ家族成员参与RPE指定。然而，我们之前提出，从表面外胚层释放的骨形态发生蛋白（BMP）对于雏鸡的 RPE 规范至关重要。我们现在表明，RPE 规范需要表达 BMP 和 Wnt 的表面外胚层。我们发现来自上层表面外胚层的 Wnt 信号传导参与限制 BMP 介导的 RPE 规范至背侧视神经泡。 Wnt2b 在背侧表面外胚层中表达，随后在背侧视神经泡细胞中表达。通过在视泡阶段植入 Wnt3a 浸泡的珠子或抑制 GSK3 β 来激活 Wnt 信号传导，抑制 NR 发育并将整个视泡转化为 RPE。在早期视泡阶段去除表面外胚层或抑制 Wnt，但不抑制 Wnt/β-连环蛋白，信号传导可防止色素沉着并下调 RPE 调节基因 Mitf。 BMP 或 Wnt 信号传导的激活可以替代表面外胚层以挽救 MITF 表达和视杯形成。我们提供的证据表明，BMP 和 Wnt 在 pSmad 水平上通过 GSK3 β 依赖但不依赖 β-连环蛋白的途径合作，以确保背侧视神经泡细胞中的 RPE 规范。我们提出了一种新的视神经泡模式的背腹侧模型，其中最初表面外胚层衍生的Wnt信号传导通过BMP信号传导的稳定作用引导背侧视神经泡细胞发育成RPE。
The retinal pigment epithelium (RPE) is indispensable for vertebrate eye development and vision. In the classical model of optic vesicle patterning, the surface ectoderm produces fibroblast growth factors (FGFs) that specify the neural retina (NR) distally, whereas TGF beta family members released from the proximal mesenchyme are involved in RPE specification. However, we previously proposed that bone morphogenetic proteins (BMPs) released from the surface ectoderm are essential for RPE specification in chick. We now show that the BMP- and Wnt-expressing surface ectoderm is required for RPE specification. We reveal that Wnt signalling from the overlying surface ectoderm is involved in restricting BMP-mediated RPE specification to the dorsal optic vesicle. Wnt2b is expressed in the dorsal surface ectoderm and subsequently in dorsal optic vesicle cells. Activation of Wnt signalling by implanting Wnt3a-soaked beads or inhibiting GSK3 beta at optic vesicle stages inhibits NR development and converts the entire optic vesicle into RPE. Surface ectoderm removal at early optic vesicle stages or inhibition of Wnt, but not Wnt/beta-catenin, signalling prevents pigmentation and downregulates the RPE regulatory gene Mitf. Activation of BMP or Wnt signalling can replace the surface ectoderm to rescue MITF expression and optic cup formation. We provide evidence that BMPs and Wnts cooperate via a GSK3 beta-dependent but beta-catenin-independent pathway at the level of pSmad to ensure RPE specification in dorsal optic vesicle cells. We propose a new dorsoventral model of optic vesicle patterning, whereby initially surface ectoderm-derived Wnt signalling directs dorsal optic vesicle cells to develop into RPE through a stabilising effect of BMP signalling.