FGF-4 REPLACES THE APICAL ECTODERMAL RIDGE AND DIRECTS OUTGROWTH AND PATTERNING OF THE LIMB

The apical ectodermal ridge plays a key role in limb development. We s how 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 dis tal mesenchyme and maintains a signal from the posterior to the distal mesenchyme that appears to be required for elaboration of skeletal el ements in the normal proximodistal sequence. Moreover, retinoic acid, which is capable of providing polarizing activity, can supply this sig nal. This suggests that polarizing activity plays a role in patterning along the proximodistal axis, in addition to its well-established rol e in anteroposterior patterning. Taken together, the data suggest a si mple mechanism whereby FGF-4 links growth and pattern formation during limb development.