Müller glia subtypes define neuro-glial associations and spatial morphogen axes in the zebrafish retina

Now Müller glia are generally accepted as transcriptionally heterogeneous, and new evidence suggests functional diversity may exist in the way these cells respond to retinal injury. It remains unclear, however, whether this functional heterogeneity is limited to a transient phenotype that stems from injury or a fundamental feature of the healthy retina.

Here, we investigate Müller glia heterogeneity in the uninjured zebrafish retina across development and adulthood using a comprehensive single-cell transcriptomic atlas of the 5 days post-fertilization (dpf) eye validated in vivo and integrated with 9 dpf and adult datasets. We reveal that Müller glia are partitioned into three constitutive subpopulations that persist from early larval stages into adulthood: 1) a proliferative and immature population in both the peripheral and central retina; 2) a novel cohort of neuron-associated Müller glia that express coherent transcriptional programs specific to distinct neuronal subtypes, including retinal ganglion, and horizontal cells; and 3) spatially distinct mature Müller glia subsets that define a dorso-ventral axis of retinoic acid metabolism, bisected by a novel cyp26c1-expressing equatorial domain.