Research Interests

Optic fissure fusion and retinal morphogenesis

Completion of retinal morphogenesis is critical for establishment of a fully functional visual system. An early critical event involves the fusion of the optic fissure, a ventral opening in the newly formed optic cup. Failure to complete this event leads to a congenital blinding disorder coloboma which is a leading cause of pediatric blindness. In our lab we are interested in the role of the hyaloid vasculature, which migrates throught the optic fissure prior to its fusion and how it may signal and facilitate the fusion process. We are currently applying single cell RNA sequencing technology to better understand the transcriptional landscape triggering optic fissure fusion.

Modeling retinal dystrophy 

Congenital and late onset retinal dystrophy are leading causes of human blindness. In out lab we are particiuarly interested in cone-rod dystrophy, where cone photoreceptors are first to be impacted therefore limiting high acuity vision, but also study RPE function in relation to retnitis pigmentosa. We recently discovered a new connnection between photoreceptor outer segments and calyceal processes (CPs) bridged by the retinal cadherins cdhr1a and pcdh15b. We are using cdhr1a mutatns to model cone-rod dystrophy and analyzing the molecular function of cdhr1a and its interacting parters including prom1b. 

Additionnally we have genereated mutant models of prph2 and are analyzing their effects on retinal homeostasis and function.

Lastly, we are also interested in merkta/tyro3 and their roles in RPE function in zebrafish as a model for MERTK-associated retnitis pigmentosa in human patients.

Formation of the ocular anterior segment

Periocular Mesenchyme (POM) are a subset of neural crest cells that ultimately generate the anterior structures of the eye, including the iris, sclera, ciliary muscles, cornea, and the trebecular mesh network.. These cells migrate along the neural crest until they encounter the retina, at which point they become strictly associated with the anterior segment region of the retina. We can visualize POM cells as they migrate to the anterior segment using a zebrafish transgenic line, FoxC1a:GFP. In contrast, we can see neural crest cell migration using the Sox10:GFP transgenic line.

While we know the ultimate purpose of the POM, we know very little of the mechanisms regulating their differentiation, migration or function. The anterior structures that arise from the POM are crucial for the function of the retina and their malfunction is associated with several ocular distrophies, including Glaucoma. However, the molecular mechanisms regulating POM differentiation and or function are largely unknown. In our lab we are therefore interested in understanding some very simple aspects of POM biology.

1) how do neural crest cells decide to become POM

2) how are POM targeted to the anterior segment

3) how do POM differentiate to form the various structures within the anterior segment

Our approach to answering these questions will involve long term time-lapse microscopy using transgenic zebrafish embryos, genomic manipulation to generate mutants and conditional knockouts for POM regulatory genes, and expression profiling of migrating POM cells.