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

Antragstellerin Dr. Astrid Vogel-Höpker
Fachliche Zuordnung Molekulare Biologie und Physiologie von Nerven- und Gliazellen
Förderung Förderung von 2010 bis 2014
Projektkennung Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 164422474
 
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.
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