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

中胚层的形成是脊椎动物发育中最早的形态发生事件之一。这一过程的特点是在分子和细胞水平上发生了一些明显的变化。中胚层祖细胞开始表达细胞类型特异性基因，并从外胚层和内胚层祖细胞中分离出来，最终形成外胚层、中胚层和内胚层三个不同的胚层。一类与中胚层形成有关的信号分子是成纤维细胞生长因子(FGFs)。FGFs及其同源受体在脊椎动物中胚层的形成中起重要作用，但目前还不完全清楚成纤维细胞生长因子信号如何控制中胚层细胞的命运和迁移。整合素是另一类与中胚层形成相关的细胞表面分子。作为细胞外基质蛋白的主要受体，它们介导与细胞外环境的黏附，并传递来自细胞内外的信号。最近的研究证实了整合素在中胚层形态发生中的需要，但整合素在这一过程中的确切作用仍不清楚。我们实验室的初步实验表明，在斑马鱼原肠形成过程中，成纤维细胞生长因子信号和整合素功能是相互依赖的，这导致了我们假设成纤维细胞生长因子受体和/或配体和整合素在这一过程中密切相互作用。在这项建议中，我们的目标是利用斑马鱼胚胎来精确地确定原肠发育过程中FGFs和整合素之间的相互关系。为此，我们将分析1)成纤维细胞生长因子和整合素在中胚层形成过程中的时空动态，2)成纤维细胞生长因子和整合素在这一过程中的相互依赖，以及3)成纤维细胞生长因子和整合素在这一过程中的遗传和分子相互作用。我期望这些实验将有助于更好地理解FGFs和整合素对中胚层形态发生的时空调控。

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.