Objective
We propose to investigate the embryological and molecular mechanisms involved in the early steps of vertebrate eye determination. A key feature of our programme is the complementary use of different vertebrate species (frog, Xenopus laevis; zebrafish, Danio rerio; medaka fish, Oryzias latipes; chick) to address the conserved aspects of eye development. Our specific aims are the following: a) We will search for new genes involved in the specification of the eye field. This will be addressed by performing differential screenings with normal and eyeless fish (wild type vs. masterblind zebrafish; wild type vs. knubbelkopf medaka) and Xenopus explants (eyed embryoids vs. eyeless embryoids). Homologues for new genes found in each of these screens will be cloned in the other model systems. b) We will then attempt to establish the functions of novel and known genes that control eye formation, by examining the phenotypes and possible epistatic relationships between the different genes by interfering with the expression and function of each gene by means of RNA or DNA micro injections (fish and frogs) or through the use of retroviruses (chicks). In these studies, we will also analyse the function and the relationships of Rxl, Six3, Eya, Pax6, ET, Otx2, whose expression during eye development has been already documented. c) We will look for new genes specifically involved in the early subdivision of the optic vesicles into the neural retina, pigment epithelium and optic stalks. We will take advantage of the large size of the chick optic vesicles and exploit two fish mutants (the medaka eyes lack, which lacks the distal parts of the developing optic vesicle and the zebrafish cyclops, which conversely lacks medial structures) to perform differential screens. These will lead to the identification of genes potentially required for the specification of the optic vesicle compartments. d) There is evidence that the subdivision of the optic vesicle is co-ordinated by diffusible factors produced by structures adjacent to the eye. We will further analyse whether members of the BMP, FGF and HH families of diffusible factors (whose expression is localized in the eye region) participate in the determination of the pigment epithelium, neural retina, and optic stalk. Their activity shall be tested by culturing optic vesicles in the presence or absence of such factors and, to complement this analysis, the role of these factors will be addressed by loss or gain of function experiments using misexpression of wild type or dominant negative variants of the wild type factors in-vivo. It is expected that the results of this research will provide a better understanding of how the vertebrate eye is formed. Since eye development in all vertebrates appears to follow the same rules, this knowledge may be extended to humans.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences genetics DNA
- medical and health sciences clinical medicine ophthalmology
- natural sciences biological sciences genetics RNA
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
CB2 3DY Cambridge
United Kingdom
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