Differentiation timing-dependent axon targeting and subtype specification in retinal ganglion cells

Subtypes of retinal ganglion cells (RGCs) in the mouse retina are each tuned to particular visual features and contribute to parallel visual processing in the brain. We addressed how RGCs are specified into distinct and diverse subtypes based on their differentiation timing. We used a neurogenic tagging mouse line, Neurod1 CreER (D1B), in which tamoxifen-inducible CreER was driven by a putative Neurod1 enhancer. Timed tamoxifen injection in this mouse line induced CreER-loxP recombination in neurons that shared the same differentiation timing. This analysis revealed that RGC axon projections to the lateral geniculate nucleus and medial terminal nucleus were segregated depending on the stage of tamoxifen injection. We further characterized the properties of these neurogenically tagged RGCs based on their molecular markers and morphological features. Our study extends the concept that differentiation timing is linked to the specification of RGC subtypes.