Transcriptional priming in neuronal diversification

Through her project Transcriptional priming in neuronal diversification, IMP group leader Luisa Cochella aims to understand the gene regulatory principles underlying the specification of cell types in an animal during embryonic development. In order to generate the many different cell types that form an animal from a single genome, each cell has to express a distinct set of genes, encoding specific structural and functional components that make each cell type unique. The expression of these gene sets is controlled by transcription factors that typically act in a combinatorial way, with two or more factors acting together to activate expression of a gene. The combinatorial activity of transcription factors enables the production of a large cellular diversity. Cochella and colleagues had previously described a novel mode of combinatorial activity of transcription factors, in which two transcription factors act on a gene at different timepoints during the development of a cell, several cell divisions apart. The first transcription factor primes the gene and the second can then boost its expression a few cell divisions later. This mechanism enables a new dimension in which transcription factor activity can be combined to increase cellular diversity. One example is the generation of morphologically symmetric pairs of neurons with asymmetric properties in the brain of the nematode worm C. elegans. But this mechanism likely acts in multiple developmental contexts, for example in the vertebrate retina in which different progenitor cells are primed early in development, biasing them towards the production of different types of retinal cells. The project of Luisa Cochella aims to illuminate our understanding of the mechanism and impact of transcriptional priming on the generation of neuronal diversity during development. Cochella and her Team will address this using C. elegans, a unique experimental system with a well-defined nervous system and a fully mapped developmental cell lineage. Apart from generating valuable knowledge for future research, the results will also be important for current efforts to directly generate different cell types in vitro.

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