Identification of ectodermal signaling pathways during the initial stages of chick eye development

脊椎动物眼睛发育的启动是几个组织之间复杂的、相互作用的结果。视泡的神经上皮细胞最初是无法区分的，共表达许多转录因子，这些细胞有能力发育成神经视网膜(NR)、视网膜色素上皮(RPE)和视柄。关于表面外胚层的功能以及导致远端视泡细分为NR和RPE结构域的分子机制，人们知之甚少。除了表面外胚层参与晶状体的形成和NR的诱导外，我们最近提出，表面外胚层在诱导RPE的发展中还有额外的作用。骨形态发生蛋白(BMP)、骨形成蛋白(WNT)和成纤维细胞生长因子(FGF)家族成员在远端视泡形成NR和RPE结构域时在表面外胚层表达，这与这些信号通路之间的相互作用提供了决定细胞分化类型的机制的观点是一致的。利用发育中的鸡胚胎，有可能将成熟的胚胎学操作与遗传操作结合起来，例如基因的错误和过度表达以及基因失活。重要的是，这样的操作可以在时间和空间上精确地定位，以剖析出前信号和内在信号的单独功能，这些信号在眼睛发育的紧密时间点上扮演着多种角色。识别内源性作用于眼睛形成的细胞和分子机制将大大增加我们对脊椎动物胚胎学的理解，特别是对眼睛发育的理解。这些结果可能为开发治疗主要致盲疾病的新疗法提供基础，如视网膜色素变性、老年性黄斑变性和糖尿病视网膜病变。

Initation of vertebrate eye development is the result of a complex, reciprocal interaction between several tissues. Neuroepithelial cells of the optic vesicle are initially indistinguishable, coexpressing a number of transcription factors and these cells are competent to develop into neural retina (NR), retinal pigment epithelium (RPE) and optic stalk. Little is known about the functions of the surface ectoderm and the molecular mechanisms that lead to the subdivision of the distal optic vesicle into a NR and RPE domain. Besides the involvement of the surface ectoderm in lens formation and NR induction, we recently proposed that the surface ectoderm has an additional role in also inducing the development of the RPE. Bone morphogenetic Protein- (BMP), WNT- and Fibroblast Growth Factor (FGF) - family members are expressed in the surface ectoderm at the time the distal optic vesicle is patterned into a NR and RPE domain, consistant with the view that a cross-talk between these signaling pathways provides a mechanism that determines the type of cell differentiation. Using the developing chick embryo it is possible to bring together well-established embryological manipulations with genetic manipulations, such as mis- and overexpression of genes and gene inactivation. Importantly, such manipulations can be precisely targeted in time and space to dissect out the individual functions of ex- and intrinsic signals that play multiple roles during closely spaced time points of eye development. Identifying the cellular and molecular mechanisms that act endogenously in eye formation would significantly increase our understanding of vertebrate embryology in general and of eye development in particular. These results potentially provide the basis for the development of novel therapeutical approaches for the treatment of major blinding diseases, such as retinitis pigmentosa, aged-related macular degeneration and diabetic retinopathy.