Researchers report finding evidence that during development, multipotent progenitor cells become committed to retinal ganglion cell fate due to the transcription factor Brn3b. They also revealed that Brn3b represses expression of transcription factors that specify alternative fates.
The scientists used microarrays to find differences in gene expression between Brn3b-null and heterozygous mice. They discovered that many of the most highly upregulated genes in null mice encoded transcription factors known to specify other retinal cell types.
Examination of cell-type-specific markers by immunostaining suggested that Brn3b-null retinas had fewer ganglion cells and many more amacrine and horizontal cells than controls. On the other hand, overexpression of Brn3b in embryonic retinas increased the proportion of ganglion cells and reduced the number of amacrine and horizontal cells.
Thus Brn3b appears to specify retinal ganglion cell fate but also prevents transdifferentiation into other retinal cell types, the team explains.
Researchers who carried out the study are from the Center for Advanced Biotechnology and Medicine and the program for molecular genetics and microbiology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey. The findings are published in March 26 issue of The Journal of Neuroscience.