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.
Ding
Hao
H
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada.
Wu
Xiaoli
X
Boström
Hans
H
Kim
Injune
I
Wong
Nicole
N
Tsoi
Bonny
B
O'Rourke
Meredith
M
Koh
Gou Young
GY
Soriano
Philippe
P
Betsholtz
Christer
C
Hart
Thomas C
TC
Marazita
Mary L
ML
Field
L L
LL
Tam
Patrick P L
PP
Nagy
Andras
A
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
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