EFFECT OF FIBROBLAST GROWTH-FACTORS ON OUTGROWTH OF FACIAL MESENCHYME

The ectoderm is required for outgrowth of facial prominences and facia l ectoderm from all facial prominences is interchangeable. Signals pro vided by the ectoderm may include members of the fibroblast growth fac tor family (FGF). In order to test whether FGFs could replace facial e ctoderm and promote outgrowth, stage 24 frontonasal mass or mandibular mesenchyme was grafted to a host chick limb and a bead soaked in FGF- 2 or FGF-4 was placed on top of the mesenchyme. Following 7 days of in cubation, the amount of outgrowth was quantified by measuring the rods of cartilage that formed from the grafts. FGF-2 and FGF-4 stimulated an increase in length of cartilage rods in mandibular grafts compared to mandibular mesenchyme grafted without ectoderm (P < 0.05). FGF-4 st imulated a small increase in length of frontonasal mass mesenchyme (P < 0.05) and both FGFs increased the frequency of egg tooth formation i n frontonasal mass mesenchyme compared ba to frontonasal mass mesenchy me grafted without ectoderm. FGFs can partially but not completely rep lace facial ectoderm since homotypic recombinations of frontonasal mas s and mandibular tissues were significantly longer than mesenchyme gra fts treated with FGF-soaked beads (P < 0.05). The addition of a second FGF-soaked bead did not significantly increase the length of the fron tonasal mass or the mandibular mesenchyme. We have determined that FGF -2 protein is expressed in facial ectoderm and could be an endogenous signal for outgrowth. In contrast, FGF-8 transcripts are not expressed in the ectoderm covering the areas of the face that were grafted; thu s, it is less likely that FGF-8 is required for outgrowth. Our results indicate that FGFs are part of an endogenous signaling pathway involv ed in distal outgrowth and chondrogenesis of the facial prominences. ( C) 1997 Academic Press.