Tesis doctoral de Flora Llense
Nowadays, it is a big challenge to understand how signalling pathways becomes activated (or inhibited) at particular times and places in developmental processes. Further, how they eventually regulate adequate cellular responses by controlling the expression of their target genes. The jnk signalling pathway is a key regulatory element of epithelial morphogenesis and cell migration involved in multiple cross-regulatory interactions. A key element in jnk signalling is puckered, an immediate early gene responding to jnk activity and, itself a negative regulator of the pathway. A promoter analysis of potential regulatory sequences of puckered identifies an enhancer specific for border cell expression during drosophila oogenesis. Collective-cell movement is a mechanism for invasion identified in many developmental events. One key model to study collective migration is the movement of border cell clusters in drosophila during oogenesis. The signalling events directing the specification and guidance of border cells have been fairly explored. However, how border cells are held together while migrate is not known. Here we show that cdc42 triggers a negative loop controlling jnk activity that regulates border cells cluster integrity. The jnk cascade hits multiple effectors, particularly the polarity determinant bazooka and the cytoskeleton adaptor d-paxillin. These effectors shape the contacts in between border cells (via de-cadherin) and border cell-substrate attachments (via íY-lntegrin) allowing and sustaining collective migration and cluster invasiveness. As highlighted in these analyses, the level of jnk activity has to be strictly regulated. Therefore, to finely dissect the temporal and spatial control of signalling events it is crucial to build new tools for sensing their activity in vivo. By using intramolecular fret, we have designed a specific sensor for jnk activity. This sensor has allowed us to identify a series of new regulators of jnk activity in migratory cells by performing different functional rnai high throughput screenings. We have linked these analyses to quantitative morphological profiling rnai methods to systematically investigate the role of individual genes in the regulation of cell morphology.
Datos académicos de la tesis doctoral «The regulatory role of the jnk signaling cascade in cell migration during morphogenesis in drosophila«
- Título de la tesis: The regulatory role of the jnk signaling cascade in cell migration during morphogenesis in drosophila
- Autor: Flora Llense
- Universidad: Barcelona
- Fecha de lectura de la tesis: 31/03/2008
Dirección y tribunal
- Director de la tesis
- Enrique Martín Blanco
- Tribunal
- Presidente del tribunal: emilio Salo boix
- darren Gilmour (vocal)
- denise Montell (vocal)
- jordi Casanova (vocal)