Research interests

The vertebrate eye emerges from an epithelial Anlage by inductive interactions beginning at late gastrula stages. Under the influence of midline signalling during neurulation, the single retina Anlage is split into two retinal primordia localised as pre-evaginated domains in the lateral wall of the prosencephalon. The subsequent evagination of the primordia is driven by the migration of individual cells into the forming optic vesicle. It results in the formation of optic vesicles that differentiate to the seven cell types of the neural retina, the retinal pigmented epithelium and the optic stalk respectively. In anamniotes [fish, amphibia], the ciliary margin of the neural retina contains a stem cell population that gives rise to all retinal cell types and facilitates lifelong growth of the eye. We investigate vertebrate [medaka, zebrafish] eye development following three complementary experimental strategies: functional studies involving large scale mutagenesis screens and mutant analysis; functional analyses involving gain- and loss-of-function analysis by ectopic expressing of transgenes in the developing eye or by blocking gene function using the morpholino knock-down technique; and in vivo analysis of retinal morphogenesis and differentiation using 4D microscopy on transgenic lines stably expressing green fluorescent protein [GFP] in different substructures of the retina. Future projects and goals For the study of retinal differentiation, regeneration and retino-tectal projection we incorporate bioinformatics as a novel tool to exploit the resources provided with the publication of the medaka genome. We plan to take advantage of the situation in fish that exhibit life-long growth of the retina and correspondingly, the optic tectum. This requires a close control of the balance between proliferation and differentiation. Addressing and understanding that in the context of fish will shed light onto the situation in amniotes, where retinal stem cells are not found in distinct domains. The maintenance of the topographic retino-tectal projection of a growing retina and tectum requires re-connectivity in the optic tectum. We plan to set up subtle genetic screens to address this question that again is of major bio-medical relevance. Mutants and other tools established in the lab are currently analysed with the aim of understanding the path that neural progenitors cells take towards terminal differentiation under conditions of growth and regeneration.



Methods applied

Analysis of mutants affecting all stages of retinal development, gain and loss of function analysis in vivo, in vivo 4D microscopy to visualize key steps in development and correlate them with functional decisions on the sepcification of retinal progenitor cells