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Endogenous epidermal growth factor regulates limb development

C Canoun1, C Ma, D Halpern

  • 1Center for Craniofacial Molecular Biology, School of Dentistry, University of Southern California, Los Angeles 90033.

The Journal of Surgical Research
|June 1, 1993
PubMed
Summary
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Epidermal Growth Factor (EGF) signaling is crucial for mammalian limb development. This study shows EGF is essential for cartilage formation and regulates embryonic forelimb morphogenesis.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Genetics

Background:

  • Mutations in Epidermal Growth Factor (EGF) superfamily genes are linked to limb malformations.
  • EGF-mediated signal transduction may play a role in early mammalian limb development.

Purpose of the Study:

  • To investigate the role of EGF precursor gene transcription and translation in embryonic limb development.
  • To determine if EGF signaling influences cartilage morphogenesis in mammalian forelimbs.

Main Methods:

  • Developed an in vitro system for limb morphogenesis and cytodifferentiation in defined medium.
  • Utilized mRNA phenotyping to detect EGF transcripts in mouse embryonic forelimbs.
  • Employed tyrphostin (RG 50864) to inhibit EGF receptor kinase activity.

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Main Results:

  • EGF mRNA transcripts were detected in embryonic mouse forelimbs.
  • EGF precursor polypeptides were localized to limb epithelium and mesenchymal cells.
  • Inhibition of EGF receptor kinase activity with tyrphostin significantly retarded limb development.

Conclusions:

  • Endogenous EGF or EGF-like proteins are critical for signaling in embryonic forelimb cartilage formation.
  • EGF signaling influences the timing and positional information required for limb-specific cartilage morphogenesis.
  • This study supports the hypothesis that EGF is vital for regulating the size and shape of forelimb cartilage during embryonic development.