Objetivo
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.
Ámbito científico
- natural sciencesbiological sciencesneurobiology
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomics
- natural sciencesphysical sciencesopticsmicroscopysuper resolution microscopy
- natural sciencesbiological sciencesevolutionary biology
- natural sciencesbiological scienceszoologyinvertebrate zoology
Programa(s)
Régimen de financiación
ERC-ADG - Advanced GrantInstitución de acogida
69117 Heidelberg
Alemania