Fgf-10 is required for both limb and lung development and exhibits striking functional similarity to Drosophila branchless

  1. Hosung Min1,
  2. Dimitry M. Danilenko2,
  3. Sheila A. Scully2,
  4. Brad Bolon2,
  5. Brian D. Ring2,
  6. John E. Tarpley2,
  7. Margaret DeRose1, and
  8. W. Scott Simonet1,3
  1. Departments of 1Molecular Genetics and 2Pathology, Amgen, Inc., Thousand Oaks, California 91320-1789 USA

Abstract

Fgf-10-deficient mice (Fgf-10−/− ) were generated to determine the role(s) of Fgf-10 in vertebrate development. Limb bud initiation was abolished inFgf-10−/− mice. Strikingly,Fgf-10−/− fetuses continued to develop until birth, despite the complete absence of both fore- and hindlimbs. Fgf-10 is necessary for apical ectodermal ridge (AER) formation and acts epistatically upstream of Fgf-8, the earliest known AER marker in mice.Fgf-10−/− mice exhibited perinatal lethality associated with complete absence of lungs. Although tracheal development was normal, main-stem bronchial formation, as well as all subsequent pulmonary branching morphogenesis, was completely disrupted. The pulmonary phenotype ofFgf-10−/− mice is strikingly similar to that of the Drosophila mutant branchless, anFgf homolog.

Keywords

Footnotes

  • 3 Corresponding author.

  • E-MAIL ssimonet{at}amgen.com; FAX (805) 447-1982.

    • Received July 23, 1998.
    • Accepted August 2, 1998.
| Table of Contents

Life Science Alliance