The aim of this proposal is to investigate the path of differentiation of retinal precursor cells in the vertebrate eye, using both medaka and zebrafish as model organisms. The neurons andglia of the retina all develop from a population of dividing precursor cells which have the potential to differentiate into any one of the cell types making up the mature retina.
As precursor cells undergo terminal differentiation, they must coordinate cell fate choice with morphological changes so that the appropriate cells are formed in the correct position within the retina. Little is understood about how this is achieved in vivo. I propose to mark precursor cells with fluorescent proteins and use time-lapse confocal microscopy to follow precursor cells in the living embryo as they differentiate, in order to better understand the morphological and other changes that cells must undergo as they mature.
This should give us a detailed picture of how retinal cells differentiate into functional neurons: a picture, which is currently lacking in the field. I also intend to approach the problem of how the retina is formed from a genetic perspective, using medaka mutants generated in the host laboratory. A number of mutants with retinal defects have been identified, whose molecular nature is unknown. I will map and clone one or more of these mutants, thus identifying new genes required for retinal development. This proposal will provide me with a wide range of new skills, which will be invaluable to me in my scientific career.
In making the switch from Drosophila to fish, I will broaden my knowledge of developmental biology, and learn a set of new techniques for the study of vertebrate development and genetics. In addition, the scientific community of EMBL will provide a stimulating atmosphere in which to do research, from which I will benefit greatly.
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