The Interplay of FGF signalling and Integrins in mesoderm formation during zebrafish gastrulation

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Mesoderm formation is one of the first morphogenetic events in vertebrate development. This process is characterised by a number of distinct changes on the molecular and cellular level. Mesoderm progenitor cells begin to express cell type-specific genes and segregate from ectoderm and endoderm progenitor cells, eventually leading to the formation of three distinct germ layers ectoderm, mesoderm and endoderm. One class of signalling molecules implicated in mesoderm formation are the Fibroblast Growth Factors (FGFs). FGFs and their cognate receptors are known to be important for mesoderm formation in all vertebrates; however, it is not yet fully clear how FGF signals control both mesoderm cell fate specification and migration.Integrins represent another kind of cell surface molecules that are associated with mesoderm formation. As principal receptors for Extracellular Matrix proteins they mediate adhesion to the extracellular environment and transduce signals from both inside and outside the cell. Recent studies demonstrated the requirement of Integrins for mesoderm morphogenesis, but how Integrins precisely function in this process remains unclear.Preliminary experiments in our lab suggest an interdependence of FGF signalling and Integrin function in mesoderm formation during zebrafish gastrulation, which led us to the hypothesis that FGF receptors and/or ligands and Integrins closely interact in this process. In this proposal, we aim to utilise zebrafish embryos to precisely determine the interrelation between FGFs and integrins during gastrulation. To this end, we will analyse i) the spatiotemporal dynamics of FGF and Integrin activity and function during mesoderm formation, ii) the interdependence of FGFs and Integrins in this process and iii) the genetic and molecular interactions of FGFs and Integrins therein. I expect that these experiments will lead to a better understanding of the spatiotemporal control of mesoderm morphogenesis by FGFs and Integrins.