Cdon acts as a Hedgehog decoy receptor during proximal-distal patterning of the optic vesicle.
Cdon acts as a Hedgehog decoy receptor during proximal-distal patterning of the optic vesicle.
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DOI：
10.1038/ncomms5272
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发表时间：
2014-07-08
影响因子：
16.6
通讯作者：
Bovolenta, Paola
中科院分区：
文献类型：
--
作者：
Julian Cardozo, Marcos;Sanchez-Arrones, Luisa;Sandonis, Africa;Sanchez-Camacho, Cristina;Gestri, Gaia;Wilson, Stephen W.;Guerrero, Isabel;Bovolenta, Paola
脊椎动物视泡的图案成近端/视柄和远端/神经视网膜涉及中线衍生的刺猬（Hh）信号，这促进柄规格。在没有Hh信号的情况下，柄没有指定，导致独眼症。最近的研究表明，细胞粘附分子Cdon与Hh受体Patched 1（Ptc 1）形成异聚复合物。该受体复合物结合Hh并增强信号传导激活，表明Cdon正调控该途径。在这里，我们表明，在发育中的斑马鱼和小鸡视泡中，cdon和ptc 1以互补模式表达，Cdon充当负Hh信号调节因子。Cdon主要定位于神经上皮细胞的基底外侧，促进神经上皮基底端足的扩大并捕获Hh蛋白，从而限制其分散。这种不依赖于Ptc的功能保护视网膜原基免受Hh活性的影响，限定了柄/视网膜边界，从而限定了眼睛的正确的近端-远端图案。 脊椎动物细胞表面糖蛋白Cdon的果蝇同源物结合Hedgehog配体，从而防止其扩散。在这里，作者为脊椎动物视泡图案形成过程中的类似机制提供了证据，其中Cdon作为Hedgehog信号传导的负调节剂，以定义视柄和视网膜之间的边界。
Patterning of the vertebrate optic vesicle into proximal/optic stalk and distal/neural retina involves midline-derived Hedgehog (Hh) signalling, which promotes stalk specification. In the absence of Hh signalling, the stalks are not specified, causing cyclopia. Recent studies showed that the cell adhesion molecule Cdon forms a heteromeric complex with the Hh receptor Patched 1 (Ptc1). This receptor complex binds Hh and enhances signalling activation, indicating that Cdon positively regulates the pathway. Here we show that in the developing zebrafish and chick optic vesicle, in which cdon and ptc1 are expressed with a complementary pattern, Cdon acts as a negative Hh signalling regulator. Cdon predominantly localizes to the basolateral side of neuroepithelial cells, promotes the enlargement of the neuroepithelial basal end-foot and traps Hh protein, thereby limiting its dispersion. This Ptc-independent function protects the retinal primordium from Hh activity, defines the stalk/retina boundary and thus the correct proximo-distal patterning of the eye. The Drosophila homologue of the vertebrate cell surface glycoprotein Cdon binds Hedgehog ligand and thereby prevents its diffusion. Here, the authors provide evidence for a similar mechanism during vertebrate optic vesicle patterning, where Cdon acts as a negative regulator of Hedgehog signalling to define the boundary between the optic stalk and the retina.
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