FGF-4 replaces the apical ectodermal ridge and directs outgrowth and patterning of the limb

Cell. 1993 Nov 5;75(3):579-87. doi: 10.1016/0092-8674(93)90391-3.


The apical ectodermal ridge plays a key role in limb development. We show that recombinant FGF-4 can substitute for the ridge to provide all the signals necessary for virtually complete outgrowth and patterning of the chick limb. FGF-4 stimulates proliferation of cells in the distal mesenchyme and maintains a signal from the posterior to the distal mesenchyme that appears to be required for elaboration of skeletal elements in the normal proximodistal sequence. Moreover, retinoic acid, which is capable of providing polarizing activity, can supply this signal. This suggests that polarizing activity plays a role in patterning along the proximodistal axis, in addition to its well-established role in anteroposterior patterning. Taken together, the data suggest a simple mechanism whereby FGF-4 links growth and pattern formation during limb development.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bone and Bones / embryology
  • Chick Embryo
  • Drug Synergism
  • Ectoderm / metabolism*
  • Embryonic Induction*
  • Extremities / embryology*
  • Fibroblast Growth Factor 4
  • Fibroblast Growth Factors / pharmacology*
  • Mesoderm / drug effects*
  • Models, Biological
  • Proto-Oncogene Proteins / pharmacology*
  • Tretinoin / pharmacology


  • Fibroblast Growth Factor 4
  • Proto-Oncogene Proteins
  • Tretinoin
  • Fibroblast Growth Factors