Gene expression is precisely controlled in time and space during the development of Metazoan organisms. While numerous studies have established how spatial information is integrated by gene regulatory regions, called enhancers, little is known about the temporal aspects of transcription. Most of our insights into gene regulation stem from the use of fixed preparations where timing is artificially reconstituted from different snapshots. Our goal is to integrate the dynamic aspects of transcription to understand how coordination is achieved and whether it is required during development. Transcriptional coordination refers to the inter- nuclear temporal coordination in gene activation (synchrony) and homogeneity in mRNA distribution across a field of coordinately developing cells. Initially we will characterize the mechanisms of transcriptional coordination in the early Drosophila embryo, a model system which allows quantitative imaging and genetic manipulations. However our ultimate goal is to extend these analyses to later stages of development during complex tissue specification.
We are improving the newly available live imaging technique to address fundamental questions about transcriptional dynamics in a multicellular developing embryo, with three main objectives:
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Examine the effects of promoter sequence and enhancer priming on transcriptional coordination.
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Analyse the inheritance of transcriptional states from mother to daughter cells and identify the bookmarking mechanisms responsible for this memory.
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Explore the functional role of transcriptional coordination for cell fate specification during cardiogenesis.
Through the novel integration of the dynamic and quantitative aspects of transcription in a living organism, our research shall connect coordination in transcription to precision in cell specification.
Figure 1: Main objective of the labExample of specific projects/recent achievements:
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First visualization of transcriptional memory in a developing multi-cellular embryo.
By monitoring the expression of stochastically expressed transgenes in living Drosophila embryos, we could visualize and quantify the extent to which transcription is inherited from mother to daughter cells (Ferraro et al., Current Biology 2016). Descendants from active mothers activate transcription twice as fast as their neighboring nuclei.
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Investigating the mechanisms leading to transcriptional memory.
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Deciphering the cis-regulatory sequences responsible for transcriptional synchrony in the early embryo.
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Documenting the existence and functional relevance of transcriptional coordination at later stages, during cardiogenesis.
