Obiettivo
The retinal-pigmented epithelium (RPE) is a specialised tissue, crucial for the development, maintenance, and function of the vertebrate eye. In spite of its relevance in ocular function, little is known about the molecular bases of RPE determination. Some genes involved in the early development of the RPE have recently been identified (e.g. Mitf and Otx genes). However, their role in the genetic network leading to the formation of the RPE is still not understood. Here we propose to establish the molecular network underlying the determination of the RPE. We will use Medaka (Oryzias latipes) mutants generated in an ongoing large-scale mutagenesis screen, at the Kondoh Differentiation Project in Kyoto. Mutants with consistent and specific defects in RPE determination have already been identified and will be used to establish epistatic relationships with the few known molecular landmarks, using gain and loss of function experiments. This, together with the phenotypic and molecular characterisation of the mutants, the mapping within Medaka genome, and the eventual identification of the genes affected by the mutations, will be the objectives of this project. The specific aims are:
1 .- Selecting Medaka mutants with early RPE patterning defects and subsequently characterising their ocular phenotype.
2.- Establishing the functional hierarchy among genes involved in RPE determination,
3.- Mapping the mutations in the Medaka genome and identifying the candidate gene for each mutation. The interest in defining the molecular mechanism involved in RPE determination arises from the crucial role of this tissue in vertebrate eye development and consequently, from the potential application of this research in the treatment of eye diseases. Dr. Wittbrodt's laboratory is specialised in studying the molecular mechanisms underlying vertebrate eye development using Medaka fish: a model system combining experimental advantages of classical genetic, embryology and molecular biology. To have access to RPE-defective Medaka mutants and to the technological tools available in this laboratory will not only allow me to accomplish this project, but will also greatly increase my research experience. Joining Dr. Wittbrodt s group would complete my technical and intellectual fonnation in the field of developmental neuroscience. Finally, my previous experience in this area would certainly be beneficial for the team and will facilitate my integration into the host laboratory.
Campo scientifico
Argomento(i)
Data not availableInvito a presentare proposte
Data not availableMeccanismo di finanziamento
RGI - Research grants (individual fellowships)Coordinatore
HEIDELBERG
Germania