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

Nat Genet. 2004 Oct;36(10):1111-6. doi: 10.1038/ng1415. Epub 2004 Sep 7.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Abnormalities, Multiple / embryology
  • Abnormalities, Multiple / genetics
  • Animals
  • Animals, Newborn
  • Cleft Palate / embryology
  • Cleft Palate / genetics
  • Gene Expression Regulation, Developmental
  • Lymphokines
  • Mice
  • Mice, Knockout
  • Palate / embryology*
  • Phenotype
  • Platelet-Derived Growth Factor / deficiency
  • Platelet-Derived Growth Factor / genetics
  • Platelet-Derived Growth Factor / physiology*
  • Receptor, Platelet-Derived Growth Factor alpha / deficiency
  • Receptor, Platelet-Derived Growth Factor alpha / genetics
  • Receptor, Platelet-Derived Growth Factor alpha / physiology*
  • Signal Transduction
  • Spina Bifida Occulta / embryology
  • Spina Bifida Occulta / genetics


  • Lymphokines
  • Platelet-Derived Growth Factor
  • platelet-derived growth factor A
  • platelet-derived growth factor C
  • Receptor, Platelet-Derived Growth Factor alpha