NeuralCellTypeEvo SIGNED

Project "NeuralCellTypeEvo" data sheet

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 Project objective

Nervous system evolution involved multiple cellular innovations, enabling fast synaptic transmission, novel sensory modalities, and complex forms of neural connectivity. These innovations were distributed to an ever-increasing number of neural cell types, each specified and maintained by the combinatorial 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, from the birth of the first neurons to the many families of neuron types that exist today. Our emphasis will be on reconstructing the cellular diversity in the ancestor of bilaterian animals and finding the key molecular innovations that drove early nervous system complexity. Towards this aim, we will first use whole-body single-cell RNAseq, in combination with a spatial expression atlas at cellular resolution, to comprehensively characterise cell types in the model annelid Platynereis dumerilii, a genetically tractable, slow-evolving bilaterian. We will then generate and compare similar datasets from diverse bilaterians and non-bilaterian outgroups to map the history of neuronal cell type diversification and infer the key regulatory and functional innovations that gave rise to the first bilaterian nervous system. For several such regulatory innovations, we will experimentally validate transcription factor binding to effector gene loci via superresolution microscopy and chromatin immunoprecipitation. We will also investigate neuron family-specific protein complexes, their subcellular localization, and neural functions via biochemical and proteomics approaches, correlative microscopy and loss-of-function analyses. This analysis of neuronal cell type diversity will for the first time trace the evolutionary history of nervous system complexity, unravelling when, where and how key neuronal innovations have driven the success of bilaterian nervous systems.

 Publications