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

Hao Ding1, Xiaoli Wu, Hans Boström

  • 1Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada.

Nature Genetics
|September 14, 2004
PubMed

Insights

Platelet-derived growth factor-C (PDGF-C) deficiency in mice causes severe developmental defects, including cleft palate, leading to perinatal death. PDGF-C and PDGF-A signal through PDGFR-alpha, impacting craniofacial and neural tube development.

Area of Science:

  • Developmental biology
  • Molecular biology
  • Genetics

Background:

  • Platelet-derived growth factor (PDGF) family members signal through PDGF receptors (PDGFRs).
  • PDGF-C is a ligand that signals via PDGFR-alphaalpha and PDGFR-alphabeta dimers.
  • The specific developmental roles of PDGF-C are not fully elucidated.

Purpose of the Study:

  • To investigate the developmental functions of PDGF-C in vivo.
  • To determine the signaling pathways utilized by PDGF-C during embryonic development.
  • To elucidate the role of PDGF-C in palatogenesis.

Main Methods:

  • Generation and analysis of Pdgfc knockout (Pdgfc(-/-)) mice.
  • Generation and analysis of compound Pdgfc(-/-) Pdgfa(-/-) knockout mice.
  • Phenotypic analysis of mutant embryos, including craniofacial, neural tube, and organ development.

Main Results:

  • Pdgfc(-/-) mice exhibit perinatal lethality due to feeding and respiratory issues linked to cleft secondary palate.
  • The Pdgfc(-/-) phenotype is less severe than that of Pdgfra(-/-) embryos.
  • Compound Pdgfc(-/-) Pdgfa(-/-) mutants display severe craniofacial clefts, blistering, renal, neural tube, skeletal, and vascular defects, mirroring Pdgfra loss-of-function.
  • PDGF-C signaling represents a novel, independent pathway in palatogenesis.

Conclusions:

  • Both PDGF-A and PDGF-C signal through PDGFR-alpha to regulate craniofacial, neural tube, and mesodermal organ development.
  • PDGF-C plays a crucial role in secondary palate formation through an independent signaling pathway.
  • Loss of PDGF-C function leads to severe developmental abnormalities, highlighting its importance in embryonic development.

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