MetEmbryoniC · Metabolic regulation of cell cleavages in early embryogenesis

Multicellular animals development begins with a sequence of rapid cell cycles and divisions, named cleavages, leading to the generation of a large pool of cells, from which the embryo develops. While there are several species-specific types of cleavages, the underlying processes of cell-cycle and cytokinesis, involving characteristic large-scale cytoskeletal reorganizations, are well conserved. Yet, how these processes integrate cell-intrinsic and -extrinsic signals, adapting to the rapidly changing environment of the developing embryo, remains largely unknown. An emerging concept implies cell metabolism as an important factor regulating cytoskeletal elements and, hence, cellular function. Here, I test the hypothesis that during cleavages, specific metabolic elements play an essential role in regulating the cytoskeleton.To address this hypothesis, I developed an innovative fluxomics approach for analyzing whole-embryo metabolism, combining metabolomics, transcriptomic, and real-time bioenergetics measurements in two different embryonic cleavage pattern models: ascidians and zebrafish. By combining the Heisenberg group's expertise in biomechanics and my expertise in metabolism, I will follow three main lines of research based on the whole-embryo fluxomics data: (1) Characterizing the spatiotemporal metabolic activity in the cleaving embryo; (2) analyzing the function of specific metabolic elements in cytoskeleton regulation during cleavages; and (3) determining the extrinsic factors (temperature and oxygen levels) affecting the mechano-metabolic reactions during cleavages. I expect these findings to provide insight into mechano-metabolic mechanisms that will advance our understanding of embryonic development and shed light on disease-related processes where metabolism and cell division are highly interconnected, such as cancer.