Isabel Guerrero Vega

Cell-to-cell communication is a key event during development essential for proper cell differentiation and morphogenesis, and its misregulation is one of the most prevalent causes of diseases such as cancer, malformations and neurological disorders. During the regulation of differentiation and growth several signalling molecules function as messengers between cells and are transported from producing to receptor cells. In some cases long-distance cell-cell signal communication is essential, and some of these signal molecules acts as morphogens; they act at a distance and in a concentration-dependent manner controlling the differential activation of target genes. Long-established models for the free diffusion of signalling molecules have recently been challenged by increasing evidence for cytoneme-mediated signalling, whereby specialized filopodia facilitate concentration and spatial restriction of a signal. These filopodia are known to play roles in several signalling pathways but little is known about their formation, dynamics and directional establishment. To study the role of cytonemes in cell-cell communication, we investigate Hedgehog (Hh) gradient formation. Hh has a central role in development in both vertebrates and invertebrates. Hh is also implicated in other processes, including adult stem cell maintenance, cell migration, axon guidance and cancer, in a wide range of organisms. The main aim of this offer is to analyse the role of cytonemes in cell-cell communication in the context of Hh signalling during the development of the wing imaginal discs and the adult abdominal segments.  We outline several approaches to study protrusion establishment and functionality of cytonemes, combining genetics, proteomics, cell biology, 3D in vivo imaging and mathematical modelling, to define the complex network of coordinated cues leading to cytoneme signalling and morphomechanics.