A specific requirement for PDGF-C in palate formation and PDGFR-alpha signaling.

Summary, in English

PDGF-C is a member of the platelet-derived growth factor (PDGF) family, which signals through PDGF receptor (PDGFR) alphaalpha and alphabeta dimers. Here we show that Pdgfc(-/-) mice die in the perinatal period owing to feeding and respiratory difficulties associated with a complete cleft of the secondary palate. This phenotype was less severe than that of Pdgfra(-/-) embryos. Pdgfc(-/-) Pdgfa(-/-) embryos developed a cleft face, subepidermal blistering, deficiency of renal cortex mesenchyme, spina bifida and skeletal and vascular defects. Complete loss of function of both ligands, therefore, phenocopied the loss of PDGFR-alpha function, suggesting that both PDGF-A and PDGF-C signal through PDGFR-alpha to regulate the development of craniofacial structures, the neural tube and mesodermal organs. Our results also show that PDGF-C signaling is a new pathway in palatogenesis, different from, and independent of, those previously implicated.

• Author: Hao Ding; Xiaoli Wu; Hans Boström; Injune Kim; Nicole Wong; Bonny Tsoi; Meredith O'Rourke; Gou Young Koh; Philippe Soriano; Christer Betsholtz; Thomas C. Hart; Mary L. Marazita; L. L. Field; Patrick P. L. Tam; Andras Nagy
• Publishing year: 2004
• Language: English
• Pages: 1111-1116
• Publication/Series: Nature Genetics
• Volume: 36
• Issue: 10
• Links: http://www.ncbi.nlm.nih.gov/pubmed/15361870; http://dx.doi.org/10.1038/ng1415
• Document type: Journal article
• Publisher: Nature Publishing Group
• Topic: Medical Genetics
• Keywords: Phenotype; Palate; Knockout; Mice; Lymphokines; Developmental; Gene Expression Regulation; Cleft Palate; Newborn; Multiple; Abnormalities; Animals; Platelet-Derived Growth Factor; Receptor; Platelet-Derived Growth Factor alpha; Signal Transduction; Spina Bifida Occulta
• Status: Published
• ISBN/ISSN/Other: ISSN: 1546-1718