title: A specific requirement for PDGF-C in palate formation and PDGFR-alpha signaling.
abstract: 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.
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada.
authors.forename: Hao
authors.initials: H
authors.lastname: Ding
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wu
authors.forename: Hans
authors.initials: H
authors.lastname: Boström
authors.forename: Injune
authors.initials: I
authors.lastname: Kim
authors.forename: Nicole
authors.initials: N
authors.lastname: Wong
authors.forename: Bonny
authors.initials: B
authors.lastname: Tsoi
authors.forename: Meredith
authors.initials: M
authors.lastname: O'Rourke
authors.forename: Gou Young
authors.initials: GY
authors.lastname: Koh
authors.forename: Philippe
authors.initials: P
authors.lastname: Soriano
authors.forename: Christer
authors.initials: C
authors.lastname: Betsholtz
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Hart
authors.forename: Mary L
authors.initials: ML
authors.lastname: Marazita
authors.forename: L L
authors.initials: LL
authors.lastname: Field
authors.forename: Patrick P L
authors.initials: PP
authors.lastname: Tam
authors.forename: Andras
authors.initials: A
authors.lastname: Nagy
mesh_terms: D000015:Abnormalities, Multiple / Q000196:embryology / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D002972:Cleft Palate / Q000196:embryology / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D008222:Lymphokines; D051379:Mice; D018345:Mice, Knockout; D010159:Palate / Q000196:embryology*; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D016136:Spina Bifida Occulta / Q000196:embryology / Q000235:genetics
chemical_list: D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; C075278:platelet-derived growth factor A; C411423:platelet-derived growth factor C; D020796:Receptor, Platelet-Derived Growth Factor alpha