An embryo builds a body from a single ball of cells, and this project will watch exactly how it does that, cell by cell. The problem is a fundamental gap in biology: we know that cells get assigned different fates (patterning) and that they physically reshape the embryo (morphogenesis), but we do not understand how these two processes are coordinated. Without that coordination, a body cannot form properly. This project will use advanced imaging and tension-sensing tools to track cell behaviour and mechanical forces in mouse embryos, both normal and genetically altered. It will also identify the key molecules that link cell identity to physical movement. This is fundamental science. It will not produce a drug or a device. But a deeper understanding of how tissues remodel themselves could inform future efforts to grow organs in the lab, or explain what goes wrong when development fails. Similar fundamental work on embryonic patterning has already shaped how we understand stem cell differentiation and congenital disorders.
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The overarching aim of this proposal is to understand how the foundation of the mammalian body plan is laid down during embryonic development. The diverse cells types of the body are spatially organised, or patterned. Cells have to behave in a coordinated manner and generate forces to shape the embryo as a whole i.e. undergo morphogenesis. A central question is how patterning is coordinated with morphogenesis. To address this, we will characterise in unprecedented spatiotemporal resolution cell behaviour and mechanical properties in wild-type and mutant embryos, using cutting-edge imaging and tension-sensing technologies. We will use transcriptomic and phospho-proteomic approaches to identify key molecules responsibly for coordinating patterning with morphogenesis, and test their function through genetic ablation. To elucidate how forces are generated during morphogenesis, we will use pharmacological and genetic approaches to perturb actomyosin function globally and locally. This programme will generate novel insights into the control of embryonic morphogenesis at the cellular and molecular level. It will also advance our understanding of the fundamental process of tissue remodelling and how this might be subverted in pathological situations, as well as contribute to increasing efforts at recapitulating morphogenesis in vitro.
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