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

• 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.

Nyckelord

Abnormalities; Multiple/embryology/genetics

Animals

Animals; Newborn

Cleft Palate/embryology/genetics

Gene Expression Regulation; Developmental

Mice

Mice; Knockout

Palate/*embryology

Phenotype

Platelet-Derived Growth Factor/deficiency/genetics/*physiology

Receptor; Platelet-Derived Growth Factor alpha/deficiency/genetics/*physiology

Research Support; Non-U.S. Gov't

Research Support; U.S. Gov't; P.H.S.

Signal Transduction

Spina Bifida Occulta/embryology/genetics

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)