Research Area: Genetic regulation of vertebrate eye field formation
Researchers: Yung Lyou & Reyna Martinez De Luna
Developmental defects of the eye are a common phenotype in many inherited diseases. To address these genetic disorders, an understanding of the genetic 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 have identified 210 transcripts (representing 199 unique unigenes) that are enriched in the endogenous eye field and induced by the EFTFs. We are currently characterizing these genes to determine what role they may play in early eye formation.
These experiments 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.
Research Area: Retinal stem cells and their use in healing the damaged retina
Researchers: Rene Choi & Reyna Martinez De Luna
Photoreceptor cell death is a common cause of many blinding diseases. Conversion of pluripotent cells to multipotent retinal progenitors that differentiate into functional retinal cell types in the blind eye would provide an important opportunity for treating retinal injuries and degenerations. Pluripotent cells treated with extrinsic factors express photoreceptor markers in vitro and integrate in vivo, but fail to develop inner or outer segments in the dystrophic or degenerating retina, indicating that additional approaches must be explored.
Our laboratory took an alternative, developmental approach and identified a gene set required for retinal formation during embryogenesis. We discovered the eye field transcription factors (EFTFs) are sufficient to convert pluripotent cells to a multipotent retinal lineage. Eyes formed from induced retinal progenitor cells are functional. Our long-term goal is to generate multipotent retinal progenitor cells in vitro for repairing retinal damage due to blinding diseases.
With our collaborators, we have developed an inducible and reversible model of retinal degeneration in the fast growing, comparatively simple organism, Xenopus laevis. Using these animals we plan to determine if EFTF-induced retinal progenitors can repair vision to a degenerated retina. If successful, these experiments will demonstrate that using the appropriate combination of factors, it is possible to convert pluripotent cells to multipotent retinal progenitors that can differentiate and repair blindness due to photoreceptor loss.