UC Santa Barbara

The present study examined the role of alternative splicing as a mechanism to create neuronal diversity within the developing retina. The Isl1 gene has two alternatively spliced isoforms, α and β, that are present in the developing retina. The Isl1β isoform lacks a critical portion of a protein-binding domain with which Isl1 binds to Lhx3 in a known transcriptional complex (Isl1:Lhx3:Ldb1). Developmental analysis of Isl1 expression reveals the Isl1α isoform is expressed at higher levels than Isl1β throughout development and persisting into adulthood. Isl1 isoforms are present in distinct subsets of retinal ganglion cells, with Isl1β-expressing cells being restricted to cells with soma sizes under 175μ². A luciferase assay demonstrates the Isl1β isoform is functionally distinct from Isl1α and is not capable of activating the Isl1:Lhx3:Ldb1 complex as Isl1α is. These results suggest that Isl1β containing-complexes may have unique gene targets from Isl1α and implicate the alternative splicing of Isl1 as a mechanism contributing to neuronal differentiation during retinal development.