Towards scaffoldless tissue engineering: Defining self organisation of embryonic cells into tissue structures

Self-organisation is a widespread phenomenon in biology, one such example being the striking morphogenetic movements and alterations in cell fate during gastrulation leading to a multi layered structure consisting of three distinct germ layers. A predominant morphogenetic event of gastrulation is elongation by convergent extension. Convergent extension is a key developmental process, yet little is known about the cues that drive the cellular movements responsible for this morphogenesis. Studies in Xenopus have revealed a unique opportunity to mimic and study convergent extension using an activin-induced mesodermal cell aggregate system. In this system tissue polarity was initially completely abolished and then reconstituted to recapitulate convergent extension. This project aims to define clearly the necessary and sufficient mechanisms which establish self-organization in activin treated cell aggregates giving rise to tissue elongation. This will be achieved through a combination of experimental and computational work exploring how convergent extension is cued in this system and by what mechanism this elongation takes place. Such knowledge is crucial to be able to harness these cues during tissue organisation. This will be a key step in enabling regenerative biology to reach its full therapeutic potential.