Analysis of the genetic regulation of anterior segment development in zebrafish (RPA Pilot / Seed Project)

Two of the main functional components, required for the acuity of vision, are the neural retina and the anterior segment (AS). The AS is comprised of the cornea, lens, iris and ciliary body, which are critical to collect and focus the light onto the retina. Failure in the development of the anterior segment can have severe consequences, including vision impairment, or even blindness. The key to understanding the development of AS disorders is to increase our knowledge of mechanisms governing AS formation. Especially, exploring and characterizing molecular pathways and gene regulation involved in differentiation and function of AS progenitor cells. The primary source of AS progenitor cells has been shown by fate mapping experiments in different species to be periocular mesenchyme (POM). POM in turn is derived from neural crest cells (NCC), a cell type that originates and subsequently migrates out of the neural tube upon its closure. The main trait that has been used to molecularly define POM cells, is the expression of marker genes, mainly transcription factors (TFs). However, for most of these markers it still has to be investigated, when, why and where they are expressed during POM differentiation. Recent studies from our own group, as well as others, suggest that POM cells are not simply one homologous cell group, but rather composed of a mixture of cells with different molecular identities and hence, likely different functional fates. Pinpointing the molecular mechanism regulating these fates would be a significant step forward for the field.