Species-Specific Timing of Neurogenesis

• Applicant: Professor Lazaro Centanin, Ph.D.
• Subject Area: Developmental Biology ; Developmental Neurobiology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 543848291

The path from a fertilised egg to a complete animal embryo embryo involves the coordinated formation of cell types, tissues and organs. Different fish species show a remarkable span in their overall embryonic developmental time — ranging from few days to several months — and in the development of specific organs like the retina. Two of the most used laboratory fish models, zebrafish (Danio rerio) and medaka (Oryzias latipes), display embryonic developmental times of 3 and 9 days respectively, with retinal neurogenesis starting one day earlier in zebrafish than in medaka. To explore whether organogenesis and the onset of neurogenesis are autonomously determined (genetic timing) or alternatively, coordinated at the organismal level (ontogenic timing), we have developed an assay to develop a zebrafish retina in medaka and a medaka retina in zebrafish. The approach relies on transplanting blastomeres, so the entire developmental trajectory into a neural fate occurs under the physiological influence of the alien species, where both the donor and the host retinae develop in parallel. Using inter-species transplantations, we have collected data indicating that the developmental time of neurogenesis in the retina follows a genetic program: an ectopic zebrafish retina in medaka develops retinal ganglion cells (RGCs) with zebrafish dynamics, and an ectopic medaka retina in zebrafish generates RGCs with medaka developmental time. In the present proposal we plan to exploit this experimental set up to characterise genetically and epigenetically how neurogenesis timing is controlled. We will use a bulk and scRNA-seq as well as bisulfite sequencing to uncover cell-autonomous molecular players, and will combine it with experimental embryology approaches to reveal non-autonomous contributions to a neural cell fate.

• DFG Programme: Research Grants