Retinal neuroblast migration and laminar organization requires the cytoskeletal-interacting protein Mllt11

Abstract

ABSTRACTBackgroundThe vertebrate retina is an organized laminar structure comprised of distinct cell types populating three nuclear layers. During development, each retinal cell type follows a stereotypical temporal order of genesis, differentiation, and migration, giving rise to its stratified organization. Once born, the precise positioning of cells along the apico-basal (radial) axis of the retina is critical for subsequent connections to form, relying on orchestrated migratory processes. While these processes are critical for visual function to arise, the regulators of cellular migration and retinal lamination remain largely unexplored.ResultsWe report a role for a microtubule-interacting protein, Mllt11 (Myeloid/lymphoid or mixed-lineage leukemia; translocated to chromosome 11/All1 Fused Gene From Chromosome 1q) in mammalian retinal cell migration during retinogenesis. We show that Mllt11 loss-of-function in mouse retinal neuroblasts affected the migration of ganglion and amacrine cells into the ganglion cell layer, and led to their ectopic accumulation in the inner plexiform layer.ConclusionsWe demonstrate that Mllt11 plays a critical role in the migration and lamination of neurons in the retina, and its loss impacted formation of the basal-most retinal layers.