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

  • 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

Research output: Contribution to journalArticlepeer-review

193 Scopus citations

Abstract

PDGF-C is a member of the platelet-derived growth factor (PDGF) family, which signals through PDGF receptor (PDGFR) αα and αβ 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-α function, suggesting that both PDGF-A and PDGF-C signal through PDGFR-α 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.

Original languageEnglish
Pages (from-to)1111-1116
Number of pages6
JournalNature Genetics
Volume36
Issue number10
DOIs
StatePublished - Oct 2004
Externally publishedYes

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