The vertebrate central nervous system (CNS) is composed by a large number of interconnected neurons distributed in different regions and with diverse functions. Recently, it was demonstrated that newly born neurons are generated in the adult mammalian brain that can be functionally integrated into already existing circuits. Also in fishes a peripheral structure of the retina, called ciliary marginal zone (CMZ), retains a reservoir of active stem cells that contributes to the life-long growth of the eye by adding newly born neurons, making this animal model suitable for the analysis of post-mitotic neuron generation and cell fate determination at post-embryonic stages.
The main focus of this proposed project is to understand how neurons can be generated and integrated into existing organs using the CMZ of medaka (Oryzias latipes) as a model system. The transparency of fish embryos and larvae will permit 4D microscopy observation of fluorescent molecular markers to analyse in vivo temporal aspects of the process. I will also take advantage of the bean-shaped eye (bns) mutant in which CMZ retain stem cell properties whereas differentiation is severely impaired, being an ideal mutant to study the molecular requirements for postembryonic neurogenesis.
This genetic approach will allow characterizing CMZ-growth mutants and identifying new molecules involved in its regulation, hopefully contributing to the understanding of molecular mechanisms that control neurogenesis after embryonic development. To manipulate the genetic cascades that regulate neurogenesis at post-embryonic stages is of great interest regarding the possibility to establish protocols for the treatment of neurodegenerative disorders in humans. I will profoundly benefit from learning advanced techniques such as 4D microscopy in an expertise lab; the possibility to perform this project in one of the leading European Institutes will be an invaluable step on my scientific career.
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