Cytoneme-mediated signalling in development

Intercellular signalling is fundamental to all multicellular organisms, coordinating growth and development and maintaining tissue structure and organisation. Traditionally, signals were believed to diffuse primarily from sender to receiver cells or, if membrane-bound, to act on directly adjacent cells. However, signalling filopodia called cytonemes represent a previously underappreciated delivery and receipt mechanism, allowing both local and distant signalling across tissues. We now understand that cytonemes are essential in controlling cell behaviour during development and tissue homeostasis. Although cytonemes have been observed in many cells and tissues, our understanding of their core components and how they function is still in its infancy. Our multidisciplinary team will leverage advanced imaging, genetics techniques and mathematical modelling to identify common principles and rationalise key differences relating to cytoneme signalling across animal models, contexts and pathways. We first aim to elucidate their ultrastructure underlying the mechanisms controlling cytoneme emergence and signal protein transport within. We will then identify the critical features of cytoneme contact sites (cytoneme synapses) as platforms for signal exchange. Finally, we will determine how cytoneme contacts control cell fate acquisition in complex tissues. Through cross-species and cross-pathway modelling, our findings will reveal fundamental principles relating to cellular communication during development and homeostasis.