Research Summary Index

Our research program focuses on eye development and disease using the zebrafish, Danio rerio, as a model system. The zebrafish is an ideal model through which genes necessary for visual system development and function can be identified. Zebrafish embryos are transparent during early development and their eyes are large and easily accessible. Furthermore, eye development in zebrafish is analagous to that observed in other vertebrate embryos, and their eyes are structurally similar to the human eye thereby providing an excellent model system in which one can address fundamental aspects of visual system development. Indeed many disrupted genes and pathways identified as integral to the formation of the zebrafish eye produce phenotypes that resemble disorders of the human visual system (Gross and Perkins, 2008). Thus, characterization of the molecular mechanisms of eye development in zebrafish promises to facilitate a better understanding of these human pathologies. By combining the power of forward genetic screens with the ease and utility of targeted reverse genetic studies, in vivo imaging and systems level approaches, our current research focuses on four main areas:

Ocular Morphogenesis
We have identified several zebrafish mutations that present with morphogenetic defects in eye development called colobomas. Colobomas are defined as clefts of absent tissue in the eye resulting from defects in ocular morphogenesis. Colobomas have been estimated to be present in 3-10% of blind children worldwide yet little is known with regard to how they arise. The overarching goal of our studies is to understand the molecular and cellular bases of ocular morphogenesis and how defects in this process can lead to coloboma formation.
(Images at right from http://insight.med.utah.edu.)

Lens Development and Cataracts
Congenital cataracts are responsible for roughly one-tenth of childhood blindness worldwide. We are interested in identifying genetic factors that lead to congenital cataracts when mutated, and by extension - how the proteins encoded by these genes normally function during lens development.

Formation and Function of the Retinal Pigmented Epithelium
The retinal pigemented epithelium (RPE) plays a number
of important roles during eye development as well as in
maintenance of the retina during post-embryonic stages.
We are interested in understanding both of these roles and
how defects in RPE formation or function can contribute to
blinding disorders of the eye like macular degeneration.

Proliferation and Regeneration of the Retina
We are interested in the molecular controls governing proliferation in the developing retina, and whether these controls are redeployed upon retinal injury and the stimulation of a regenerative response.