Objectif Autophagy is a fundamental cellular catabolic process deputed to the degradation and recycling of a variety of intracellular materials. Autophagy plays a significant role in multiple human physio-pathological processes and is now emerging as a critical regulator of skeletal development and homeostasis. We have discovered that during postnatal development in mice, the growth factor FGF18 induces autophagy in the chondrocyte cells of the growth plate to regulate the secretion of type II collagen, a major component of cartilaginous extracellular matrix. The FGF signaling pathways play crucial roles during skeletal development and maintenance and are deregulated in many skeletal disorders. Hence our findings may offer the unique opportunity to uncover new molecular mechanisms through which FGF pathways regulate skeletal development and maintenance and to identify new targets for the treatment of FGF-related skeletal disorders. In this grant application we propose to study the role played by the different FGF ligands and receptors on autophagy regulation and to investigate the physiological relevance of these findings in the context of skeletal growth, homeostasis and maintenance. We will also investigate the intracellular machinery that links FGF signalling pathways to the regulation of autophagy. In addition, we generated preliminary data showing an impairment of autophagy in chondrocyte models of Achondroplasia (ACH) and Thanathoporic dysplasia, two skeletal disorders caused by mutations in FGFR3. We propose to study the role of autophagy in the pathogenesis of FGFR3-related dwarfisms and explore the pharmacological modulation of autophagy as new therapeutic approach for achondroplasia. This application, which combines cell biology, mouse genetics and pharmacological approaches, has the potential to shed light on new mechanisms involved in organismal development and homeostasis, which could be targeted to treat bone and cartilage diseases. Champ scientifique engineering and technologyenvironmental engineeringwaste managementwaste treatment processesrecyclingnatural sciencesbiological sciencescell biologynatural sciencesbiological sciencesgeneticsmutationmedical and health sciencesbasic medicinephysiologyhomeostasis Mots‑clés Autophagy Lysosome Fibroblast Growth Factors Bone Cartilage Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Thème(s) ERC-2016-STG - ERC Starting Grant Appel à propositions ERC-2016-STG Voir d’autres projets de cet appel Régime de financement ERC-STG - Starting Grant Institution d’accueil FONDAZIONE TELETHON ETS Contribution nette de l'UE € 1 586 430,00 Adresse VIA VARESE 16/B 00185 Roma Italie Voir sur la carte Région Centro (IT) Lazio Roma Type d’activité Research Organisations Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 1 586 430,00 Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution nette de l'UE Tout développer Tout réduire FONDAZIONE TELETHON ETS Italie Contribution nette de l'UE € 1 586 430,00 Adresse VIA VARESE 16/B 00185 Roma Voir sur la carte Région Centro (IT) Lazio Roma Type d’activité Research Organisations Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 1 586 430,00