biostudies-literatureBonatto Paese CLNIDCR NIH HHSNational Institute of Dental and Craniofacial ResearchCincinnati Children's Hospital Medical Centerdmm049611https://www.ebi.ac.uk/biostudies/studies/S-EPMC9403750biostudies-literatureUnknown15(8)Ciliopathies represent a disease class characterized by a broad range of phenotypes including polycystic kidneys and skeletal anomalies. Ciliopathic skeletal phenotypes are among the most common and most difficult to treat due to a poor understanding of the pathological mechanisms leading to disease. Using an avian model (talpid2) for a human ciliopathy with both kidney and skeletal anomalies (orofaciodigital syndrome 14), we identified disruptions in the FGF23-PTH axis that resulted in reduced calcium uptake in the developing mandible and subsequent micrognathia. Although pharmacological intervention with the U.S. Food and Drug Administration (FDA)-approved pan-FGFR inhibitor AZD4547 alone rescued expression of the FGF target SPRY2, it did not significantly rescue micrognathia. In contrasDisease models & mechanismsPharmacological intervention of the FGF-PTH axis as a potential therapeutic for craniofacial ciliopathies.PMC9403750R35 DE027557Brugmann SAKristekova DChang CFBonatto Paese CLfalsePharmacological intervention of the FGF-PTH axis as a potential therapeutic for craniofacial ciliopathies.Ciliopathies represent a disease class characterized by a broad range of phenotypes including polycystic kidneys and skeletal anomalies. Ciliopathic skeletal phenotypes are among the most common and most difficult to treat due to a poor understanding of the pathological mechanisms leading to disease. Using an avian model (talpid2) for a human ciliopathy with both kidney and skeletal anomalies (orofaciodigital syndrome 14), we identified disruptions in the FGF23-PTH axis that resulted in reduced calcium uptake in the developing mandible and subsequent micrognathia. Although pharmacological intervention with the U.S. Food and Drug Administration (FDA)-approved pan-FGFR inhibitor AZD4547 alone rescued expression of the FGF target SPRY2, it did not significantly rescue micrognathia. In contras2022-01-01T00:00:00Z2022 Aug2025-04-19T01:36:34.125Z2025-04-07T12:21:51.961ZS-EPMC94037503581879910.1242/dmm.049611