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Seminar: Dissecting the biophysical mechanisms shaping organs during development, Dr Timothy Saunders Mechanobiology Institute, National University of Singapore

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Location: A041, Medical School Building, Gibbet Hill

Abstract: How does complex organ shape arise during development? We tackle this longstanding question using cardiogenesis in Drosophila and Zebrafish somite formation.

The ability to form specific cell-cell connections within complex cellular environments is critical for organ formation. However, the underlying mechanisms of cell matching that instruct these connections remain elusive. We quantitatively explored the dynamics and regulation of cell matching processes utilizing Drosophila cardiogenesis. We found that cell matching is highly robust at boundaries between cardioblast (CB) subtypes, and filopodia of different CB subtypes have distinct binding affinities. Further, we identified adhesion molecules Fasciclin III (Fas3) and Ten-m, both of which also regulate synaptic targeting, as having complementary differential expression in CBs. Altering Fas3 expression changes differential filopodia adhesion and leads to CB mismatch. Furthermore, only when both Fas3 and Ten-m are lost is CB alignment severally impaired. These results show that differential adhesion mediated by selective filopodia binding efficiently regulates precise and robust cell matching.

In the Zebrafish embryo, future muscle segments (myotomes) are generated from the tailbud. Each myotome forms from a somite, which is initially ellipsoidal in shape. As somites develop into muscles they form a distinctive chevron-like shape, believed to be important for swimming. We applied live imaging, 3D image analysis techniques, and biophysical modelling to explore how the distinctive Zebrafish myotome shape develops. We found that the interplay between differential spreading of somites and their coupling to surrounding tissues generates the fundamental stresses that make the chevron. Cell rearrangements within the somite are not responsible for the chevron formation but are essential in ensuring that the chevron is stable and irreversible.

Our results that show that differential forces and friction between cells and tissues are essential to generate complex shape in vivo.

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