Islet-2 Is Required for the Survival of Islet-Expressing Retinal Ganglion Cells but Not for Their Pathfinding to the...

Retinal ganglion cells (RGCs) exhibit remarkable diversity owing to their expression of developmentally expressed transcription factors. Many transcription factors are expressed in unique RGC populations, but their roles within these populations remain undiscovered. The transcription factor Islet-2 (Isl2) is expressed in approximately 30%-40% of contralateral projecting RGCs. Previous work by others found increased ipsilateral innervation of the dorsal lateral geniculate nucleus (dLGN) in Isl2 mutant mice, implicating Isl2 in promoting a contralateral RGC axon trajectory. Since Isl2 mutant mice suffer early neonatal lethality, the role of Isl2 in RGC specification has not been fully explored. To test the role of Isl2 in RGC development, two lines of retina-specific Isl2 mutant mice were generated. Contrary to the findings in Isl2 null mice, Isl2 retinal deletion does not lead to early postnatal lethality or increased ipsilateral projections to the dLGN. Instead, there is a significant reduction in the size of the dLGN and a mild reduction in the size of the ipsilateral projection to the dLGN. Retinal Isl2 mutants also exhibit diminished expression of genes characteristic of Isl2-expressing RGCs, along with increased retinal cell death during development. These findings suggest that Isl2 is required for the development and survival of Isl2-expressing RGC subtypes.