Objetivo The Hedgehog (Hh) pathway is an evolutionarily conserved signal transduction pathway recognized as a key mediator of many fundamental processes in embryonic development. It has also been implicated in a number of human diseases, ranging from different type s of cancer to developmental defects.Hh acts as a morphogen, activating different target genes depending on its extracellular concentration. A central component of the Hh pathway is the Hh receptor Patched (Ptc). Ptc controls the expression of Hh target genes by repressing Smoothened (Smo), an essential transducer of the Hh signal. Hh binding to Ptc abrogates this inhibitory effect, leading to the activation of the pathway.Although Ptc plays a central role in the Hh pathway, it is still not known how it functions, how it represses Smo and how the binding of Hh alleviates this repression. Furthermore, little is know about the mechanism that allows cells to measure and respond to different concentrations of Hh. We have followed a novel experimental approach by expressing constitutively active and inactive forms of the Hh receptor Ptc, in vivo, in the absence of the endogenous receptor and at physiologically relevant levels.This work has led to the demonstration that cells interpret Hh concentration by measuring the ratio of active (unbound to Hh) to inactive (bound to Hh) Ptc, this being the first demonstration that a morphogen gradient is read by comparing the ratio of active to inactive receptor. My future research plans include the characterization of the mechanism that allows the cells to measure the ratio between bound and unbound Ptc.The understanding of the mechanism that allow cells to measure and respond to distinct Hh concentrations is not only relevant during normal development but also for our understanding of mechanisms of diseases that involve Hh signalling. The results obtained will also help us to generate a better understanding of the precise mechanism of Ptc function. Ámbito científico ciencias naturalesciencias biológicasbioquímicabiomoléculasproteínasciencias naturalesciencias biológicasbiología del desarrollociencias médicas y de la saludmedicina clínicaoncología Palabras clave Drosophila Patched Smoothened Programa(s) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Tema(s) MOBILITY-4.2 - Marie Curie International Reintegration Grants (IRG) Convocatoria de propuestas FP6-2004-MOBILITY-12 Consulte otros proyectos de esta convocatoria Régimen de financiación IRG - Marie Curie actions-International re-integration grants Coordinador CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS (CSIC) Dirección Serrano 117 Madrid España Ver en el mapa Enlaces Sitio web Opens in new window Aportación de la UE Sin datos
