Evolution of Neuronal Cell Types at the Single Cell Level

• Applicant: Dr. Christine Mau
• Subject Area: Evolutionary Cell and Developmental Biology (Zoology)
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 536525140

The complex animal brain guides behavior by integrating external stimuli and internal states. To adapt to different life strategies, brain structure and function has been evolutionary modified leading to distinct brain morphologies. However, the cellular and genetic mechanisms of brain evolution are still unclear although adaption of brain function to environmental conditions is crucial for survival and evolution of species. Recently, the central complex (CX) in insects has become a model system to shed light on the evolution of brains. The conserved transcription factor (TF) retinal homeobox (rx) was found to be involved in CX development and rx positive cells have been marked by genome editing in both, flies and beetles. Tracing of these homologous rx genetic neural lineages found evidence for developmental divergence between Drosophila and Tribolium based on morphological studies. However, the molecular cues governing these observed differences remain unknown. In one part of my project, I want to leverage the rx genetic neural lineage to expand the scope of research to the molecular divergence on the single nuclei level. To that end, I will mark the nuclei of rx positive neurons both in Drosophila and Tribolium by using genome editing. This will allow me to apply single-nuclei RNA sequencing to analyze the gene expression profile of cells obtained from the rx genetic neural lineage. The obtained molecular neuronal cell clusters will be mapped to the 3D reconstruction of the corresponding cells. This combination of 3D brain projections and gene expression data from two species is unique in the field and will allow to identify new potential TFs responsible for the divergence of Drosophila and Tribolium brain development. Recently, rx was as well discovered as essential factor for mushroom body (MB) development in the Drosophila brain. Since rx is conserved between Drosophila and Tribolium, rx was expected to be involved in MB development in Tribolium as well. Intriguingly, it was found to remain active in the adult Tribolium MBs while it is shut down in Drosophila. Since, rx is involved in cell proliferation of MB neuroblasts in Drosophila, it could be as well essential for MB development in Tribolium. Therefore, the rx genetic neural lineage marker can be used as well to open the divergence of MBs in Drosophila and Tribolium for investigation. However, the involvement of rx in MB development in Tribolium was not studies so far. In a second part of the proposed project, I will open the developmental divergence of MBs in Drosophila and Tribolium for investigation and start by analyzing the involvement of rx in Tribolium MB development.

• DFG Programme: WBP Position