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How do cardiac cells, once specified, acquire their particular fate and function? Our research projects focuse on the molecular mechanisms of cardiac differentiation, taking advantages of Drosophila to provide a systems biology understanding of the process.
Mechanisms of cardiac differentiation
Cardiogenesis in Drosophila constitutes a well comprehended and documented example of organogenesis in which the function of a number of regulatory factors (Transcription Factors (TFs) or signaling pathways) has been thoroughly studied and described. The Drosophila cardiac system has long been recognized as homologous to the cardiovascular system of vertebrates, in particular because conserved TFs are involved in cardiac development in both fly and vertebrates. The implication of these TFs in a variety of cardiac diseases highlights the need to acquire an in depth understanding of their functions.
In the past years, our goal has been to analyse the genetic control of embryonic and adult cardiomyocytes differentiation (Perrin et al 2004: Monier et al 2005). and to set up functional genomics approaches to analyse cardiac tube formation (Zeinouti et al 2007; Salmand et al 2011). We also developed physiological and cellular approaches to analyze cardiac function, which allows measuring in vivo the functional consequences of gene invalidations (Lalevée et al 2006; Sénatore et al 2010).
Current projects aim at providing a holistic view of the genetic networks which control cardiac differentiation. How do conserved TFs dynamically interact to control the successive steps driving progressively the differentiation of the cardiomyocytes? What are the downstream gene networks controlled by these TFs? These questions are the main issues we want to tackle. The objectives are to generate and integrate genome-wide qualitative and quantitative data to dissect the GRN that dynamically controls the progressive differentiation of the cardiac system. This project is done in close collaboration with several european laboratories (see Modheart webpage).
We are also interested in investigating how effectors genes in the network produce the phenotype. Specifically, in colaboration with Nathalie Lalevée, our goal is to understand the mechanisms by which the cardiac function is acquired and regulated, in particular during mechanosensation (Sénatore et al 2010), a process in which cells sense and respond to mechanical strain.
In addition, to investigate how the cardiac function is maintained at adulthood, we have recently launched a data driven approach to unravel the genetic control of cardiac aging. This lead to the identification of several transcription factors and signalling pathways (Monnier et al, in press), whose precise function and activation during cardiac aging is currently under investigation.
These integrated approaches take advantage of our joined competences in genetics, genomics, cell biology and physiology and benefits from the bioinformatics competencies developed in the lab.