Expansion microscopy in zebrafish embryo to study primary cilia function during cardiovascular development and diseases
This project aims at revealing the function of primary cilia during cardiovascular development and cardiovascular diseases, with a specific focus on cardiac valves, through an imaging approach based on expansion light microscopy. Cilia are evolutionary conserved organelles, involved in fundamental processes such as motility, signalling and mechano-sensing, associated with a group of developmental diseases termed ciliopathies. Cardiovascular defects are common in patients diagnosed with ciliopathies and genetic studies have identified mutations in genes coding for ciliary proteins in patient suffering from congenital heart diseases, suggesting an important role for this organelle in cardiogenesis. In particular, it has been shown that DZIP1, a cilia related protein involved in ciliogenesis, is mutated in patients.  However, little is known about molecular mechanisms underlying DZIP1 abnormal function at developmental stages of valvulopathies. Using an innovative imaging-based approach in human ciliated cells and in zebrafish, we will investigate if cilia assembly, maintenance and disassembly are correlated with essential regulatory functions of DZIP1 during cardiogenesis, more precisely in endocardial cells (EdCs) during valvulogenesis. We will test if the protein DZIP1/Iguana function is not restricted to ciliogenesis in differentiated cells, but displays dynamic functions at centrioles and in the cytoplasm, that are important for tissue-remodelling. My multidisciplinary approach will allow me to tackle this question from the molecular and structural to the cellular and tissue-scale.