Cell migration and chick limb development: Chemotactic action of FGF-4 andthe AER

Experiments have been carried out to investigate the role of the apical ect odermal ridge (AER) and FGF-4 on the control of cell migration during limb bud morphogenesis. By coupling DiI cell labeling with ectopic implantation of FGF-4 microcarrier beads we have found that FGF-4 acts as a potent and s pecific chemoattractive agent for mesenchymal cells of the limb bud. The re sponse to FGF-4 is dose dependent in both the number of cells stimulated to migrate and the distance migrated. The cell migration response to FGF-4 ap pears to be independent of the known inductive activity of FGF-4 on Shh gen e expression. We investigated the role of the AER in controlling cell migra tion by characterizing the migration pattern of DiI-labeled subapical cells during normal limb outgrowth and following partial AER removal. Subapical cells within 75 mu m of the AER migrate to make contact with the AER and ar e found intermingled with nonlabeled cells. Thus, the progress zone is dyna mic with cells constantly altering their neighbor relationships during limb outgrowth. AER removal studies show that cell migration is AER dependent a nd that subapical cells redirect their path of migration toward a functiona l AER. These studies indicate that the AER has a chemoattractive function a nd regulates patterns of cell migration during limb outgrowth. Our results suggest that the chemoattractive activity of the AER is mediated in part by the production of FGF-4. (C) 1999 Academic Press.