AbstractsBiology & Animal Science

From molecular to tissue-specific roles of Fascin during Drosophila tracheal development: A link between the FGF signalling pathway and the actin-cytoskeleton

by Pilar Moyong Okenve Ramos

Institution: Universitat de Barcelona
Year: 2014
Keywords: Drosòfila; Drosophila; Tràquea; Tráquea; Trachea; Morfogènesi; Morfogénesis; Morphogenesis; Citosquelet; Citoesqueleto; Cytoskeleton; Ciències Experimentals i Matemàtiques
Record ID: 1125916
Full text PDF: http://hdl.handle.net/10803/284476


How a chemoattractant can act on a tissue to induce its migration towards that source? I have tried to answer this question in this research using as migratory tissue model the Drosophila respiratory organ (trachea) during its embryonic development and studying the role of the actin-bundling protein Fascin (called Singed in Drosophila). The tracheal system has been widely used as a model system for tubulogenesis. The formation of tubules is the main organisation of several organs in vertebrates and invertebrates that are essential for life. They allow the exchange of liquid, gas or nutrients to the corresponding target tissues. Some examples are kidney, mammary gland and vascular system in vertebrates, and in insects the salivary gland or the excretory system. The conserved FGF (Branchless -Bnl- in Drosophila) / FGFR (Breathless -Btl-) signalling pathway plays crucial roles in tracheal formation and, among other processes, it regulates branch migration through the induction of filopodia and motile properties in the leading cells. It has been largely unknown how this pathway triggers the actin-cytoskeleton reorganisation required for filopodia formation and guided migration. Fascins are an evolutionary conserved family of actin-crosslinking proteins responsible for the tight packing of parallel filaments of actin into bundles that compose several cortical cell protrusions. Filopodia are among those protrusions and they typically extend at the cell front of migratory cells to act as guiding sensors and mechanical devices to facilitate guided migration. Fascin is the primary actin crosslinker in filopodia and is essential for their formation. Fascin function has already been associated in different organisms and tissues with cell migration and adhesion. Interestingly, fascin upregulation in several carcinomas is thought to be a key factor in the metastatic process, making our study also relevant in the medical field. In Drosophila an only fascin homolog is encoded, singed (sn). Therefore I decided to test the possibility that Sn is required for tracheal migration, and the possible involvement of the Bnl/Btl pathway in its regulation. In this study I find that the tracheal chemoattractant FGF/Bnl and its pathway induce sn expression in the tracheal system, and that this regulation is functional. The functional analysis of Sn in the tissue lead to the conclusion that Sn is required for several processes mainly related to the leading cells, where Sn is highly accumulated. These cells pull the trailing cells, inducing the migration of the tissue. I specifically find that sn is required in the tissue for: timely and guided migration of the branches, fusion between branches, terminal cell specification, cell extension and terminal lumen guidance. At the cellular level, I find that Sn provides enough stiffness to the filopodia and that it controls the formation of the correct number of filopodia. The rigid filopodia have the necessary strength to push the organized cell front that extends towards the correct place. A…