Molecular Landscapes of Embryonic and Post-Embryonic Neurogenesis in the Vertebrate Retina

Abstract

Zebrafish retinas, undergoing life-long neurogenesis, provide an integrating model to resolve molecular landscapes of embryonic and post-embryonic neurogenesis. By single-cell RNAseq of zebrafish embryonic retinal progenitors and post-embryonic ciliary marginal zone (CMZ) progenitors, we define 7 distinguished states, 4 independent states (S1/S3/S5/S7) separated by 3 transitional states (S2/S4/S6), that develop over time and reveal aspects of lineage evolution. Genes that define earlier states are more critical for making retinas and post-embryonic CMZ, while genes that define later states are more critical for specifying individual cell fates. Remarkably, transitional and independent states expressed different cell-cycle phase genes, suggesting state transition relies on cell cycle. Intriguingly, similar analysis CMZ cells revealed similar set of states, suggesting embryonic and post-embryonic retinogensis conform to the same molecular program, although some interesting differences in rod genesis. Thus, our findings exemplify molecular landscapes of embryonic and post-embryonic neurogenesis in a vertebrate CNS tissue.