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

自组织在生物学中是一个广泛的现象，其中一个例子是在原肠胚形成过程中惊人的形态发生运动和细胞命运的改变，导致由三个不同的胚层组成的多层结构。原肠胚形成的主要形态发生事件是通过收敛延伸而延长。趋同扩展是一个关键的发育过程，但很少知道的线索，驱动负责这种形态发生的细胞运动。对非洲爪蟾的研究揭示了利用激活素诱导的中胚层细胞聚集系统模拟和研究趋同扩展的独特机会。在这个体系中，组织极性最初被完全废除，然后被重构为收敛扩展。本项目旨在明确定义必要和充分的机制，在激活素处理的细胞聚集体中建立自组织，从而引起组织伸长。这将通过实验和计算工作的结合来实现，探索如何在该系统中提示收敛扩展以及通过何种机制发生这种扩展。这些知识对于能够在组织组织过程中利用这些线索至关重要。这将是使再生生物学充分发挥其治疗潜力的关键一步。

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.