A gene regulatory network for retinal ganglion cell development

Differentiated cell types originate during development from precursor cells that generally have the potential to give rise to multiple cell types. Choosing an individual cell fate relies on both the precursor cell's external environment and its internal genetic program at a particular moment in time. My laboratory is investigating how gene expression programs are regulated when precursor cells differentiate into individual cell types. We are especially interested in the role of cell-type specific transcription factors and their ability to alter programs of gene expression. We use diverse models to delineate how particular transcription factors work to program cellular differentiation.

In one project using mice, we have identified some of the key transcription factors that regulate the differentiation of the ganglion cells of the neural retina. Retinal ganglion cells are responsible for transmitting electrical impulses from the retina to the primary visual centers of the brain via the optic nerve. Although retinal ganglion cells are essential for vision, how they form and why they die in retinal disease is poorly understood. We have discovered that two transcription factors play critical roles in the formation of retinal ganglion cells. A factor called Math5 is required for making precursor cells competent to advance to a retinal ganglion cell fate while a second factor called Brn3b is necessary for overt retinal ganglion cell differentiation. We have placed Math5 and Brn3b as central nodes in a genetic regulatory network responsible for retinal ganglion cell formation. Our current investigations are aimed at elaborating the network using a combination of genetic and genomic approaches.