NeuralCellTypeEvo · Cellular innovation driving nervous system evolution

Nervous system evolution involved multiple cellular innovations, enabling fast synaptic transmission,novel sensory modalities, and complex forms of neural connectivity. These innovations weredistributed to an ever-increasing number of neural cell types, each specified and maintained by thecombinatorial activity of transcription factors. When, where, and how did this complexity arise?This proposal aims at resolving the history of cell type diversification that led to this complexity, fromthe birth of the first neurons to the many families of neuron types that exist today. Our emphasis willbe on reconstructing the cellular diversity in the ancestor of bilaterian animals and finding the keymolecular innovations that drove early nervous system complexity.Towards this aim, we will first use whole-body single-cell RNAseq, in combination with a spatialexpression atlas at cellular resolution, to comprehensively characterise cell types in the model annelidPlatynereis dumerilii, a genetically tractable, slow-evolving bilaterian. We will then generate andcompare similar datasets from diverse bilaterians and non-bilaterian outgroups to map the history ofneuronal cell type diversification and infer the key regulatory and functional innovations that gaverise to the first bilaterian nervous system. For several such regulatory innovations, we willexperimentally validate transcription factor binding to effector gene loci via superresolutionmicroscopy and chromatin immunoprecipitation. We will also investigate neuron family-specificprotein complexes, their subcellular localization, and neural functions via biochemical and proteomicsapproaches, correlative microscopy and loss-of-function analyses.This analysis of neuronal cell type diversity will for the first time trace the evolutionary history ofnervous system complexity, unravelling when, where and how key neuronal innovations have driventhe success of bilaterian nervous systems.