Coordination of patterning and morphogenesis during establishment of the mammalian body plan

Year of award: 2023

Grantholders

  • Prof Shankar Srinivas

    University of Oxford, United Kingdom

Project summary

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.