Comparative Analysis of Apoptosis Gene Expression Between Brn3b–Null and Wild–Type Mouse Retinas

Abstract

Abstract: : Purpose:Retinal development follows a hierarchical gene regulatory network which specifies retinal ganglion cells (RGCs) as the first cell type to develop. This gene regulatory network involves several intrinsic transcription factors including brn3b which has been shown to be critical for normal RGC differentiation and maturation. Deletion of brn3b results in short, disorganized RGC axons as well as marked RGC cell death. Approximately 70% of RGCs from brn3b–null retinas die due to enhanced apoptosis between E15.5 and birth indicating a potential role for genes involved in apoptosis in RGC development. The purpose of our study was to identify genes involved in apoptosis that are differentially expressed in brn3b–null retinas compared with wild–type retinas. Methods: Expression levels of genes involved in apoptosis were compared between brn3b–null and wild–type retinas using the GEArray® Mouse Apoptosis Microarray system and in situ hybridization. Results:While a majority of genes involved in apoptosis were equally expressed in brn3b–null and wild–type retinas, two genes were found to be differentially expressed between the two tissue types. The two genes found to be differentially expressed were Dad1, an anti–apoptotic gene, and Bok, a proapoptotic member of the Bcl–2 family. Conclusions: These results indicate a role for the differential expression of apoptotic genes in the early brn3b regulated developmental pathway of retinal ganglion cells and their importance in early RGC survival.

Keywords: retinal development • apoptosis/cell death • transgenics/knock-outs