Differential use of a multiciliation gene module in Choroid Plexus and Cajal-Retzius neurons – BrainGem

Brain function requires the specification of distinct cell types in the appropriate numbers, place and time during development. Defects in the acquisition of either neuronal or non-neuronal identities may result in neurodevelopmental disorders. It is therefore essential to better understand the molecular regulations underpinning cell fate acquisition. Our proposal aims at understanding how two apparently unrelated cell types of the telencephalon, Cajal-Retzius cells (CR, a peculiar type of cortical neurons) and choroid plexus (ChP, epithelial multiciliated cells that secrete the cerebrospinal fluid) co-opted the same gene module to perform radically distinct cellular functions: neuronal specification vs. multiciliation. We will combine cutting-edge methodologies (single-cell transcriptomics, in utero electroporation, live imaging) with mouse genetics and histology to: (i) investigate the differential contribution of multiciliation genes to CR and ChP development; (ii) understand how a gene regulatory network can be reconfigured during evolution to perform an alternative function; (iii) determine how replicative stress might be involved in cell fate commitment and control of cell lifespan.