Function of FGF-4 in limb development.
The apical ectodermal ridge plays a central role in limb development through its interactions with the underlying mesenchyme. Removal of the AER results in cessation of limb outgrowth and leads to truncation of the limb along the proximo-distal axis. The many functions attributed to the ridge include maintenance of the progress zone mesenchyme. Here, cells are stimulated to proliferate, are maintained in an undifferentiated state, and are assigned progressively more distal positional values as the limb grows. The AER also functions to maintain the activity of the polarizing region, a region of mesenchyme which is thought to provide the primary signal for patterning along the antero-posterior axis. We have begun to explore the function of fibroblast growth factor-4 (FGF-4) during limb development. FGF-4, which encodes an efficiently secreted protein, is expressed in the AER. We have previously demonstrated that FGF-4 protein can stimulate limb mesenchyme proliferation and can induce the expression of a downstream homeobox gene, Evx-1 (homologue of the Drosophila even-skipped gene), that is normally regulated by a signal from the AER. To determine to what extent FGF-4 protein can substitute for the AER to allow normal limb outgrowth, we performed experiments on the developing chick limb in ovo. Remarkably, we find that after AER removal, the FGF-4 protein can provide all the signals required for virtually normal outgrowth and patterning of the limb.(ABSTRACT TRUNCATED AT 250 WORDS)
Niswander
L
L
Department of Anatomy and Developmental Biology, University of California, San Francisco.
Tickle
C
C
Vogel
A
A
Martin
G
G
D000818:Animals; D002642:Chick Embryo; D004475:Ectoderm / Q000502:physiology; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005121:Extremities / Q000196:embryology*; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000502:physiology*; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D014212:Tretinoin / Q000494:pharmacology; D014921:Wings, Animal / Q000196:embryology
C496446:Fgf4 protein, mouse; D051519:Fibroblast Growth Factor 4; D011518:Proto-Oncogene Proteins; D014212:Tretinoin; D005346:Fibroblast Growth Factors