Students Profiles

Developmental defects of the eye are a common phenotype in many inherited diseases. To address these genetic disorders, an understanding of the genetic regulatory network driving eye development is essential. In all vertebrates studied thus far, the eye develops from the most anterior part of the neural plate in a region known as the eye field.  Seven eye field transcription factors (EFTFs) are coordinately expressed in the eye field at the time of its specification and each is required for normal eye formation. We recently discovered that coordinated expression of the EFTFs is sufficient to divert pluripotent cells from a skin to eye field-like fate. Using this unique tool, we performed a high throughput DNA microarray screen to identify EFTF targets required for eye formation. We identified 218 transcripts (representing 181 genes) that are enriched in the endogenous eye field and induced by the EFTFs. We then performed a series of single gene validation studies using real time RT-PCR and whole mount in situ hybridization (WISH) to confirm the microarray results. Four genes were selected for further characterization. Eye Primordia Genes (EPG) 29, 140, 147, and 185 are induced by the EFTFs, expressed in the developing eye, have no known functional motif, yet have been evolutionarily conserved. Future studies will focus on determining the developmental expression patterns, regulation and potential functions of these four genes. Characterization of these and the other genes identified in this screen, should identify common, conserved developmental mechanisms, new and potentially disease causing genes, and could lead the way toward new and innovative approaches for preventing and treating blinding diseases.