FGF-8 INFLUENCES CELL MOVEMENTS AND GENE-EXPRESSION DURING LIMB DEVELOPMENT

FGF-2 is proposed to be an important ectodermal signal directing limb outgrowth and patterning. Consistent with this hypothesis we show that ectopic application of FGF-2 can maintain the apical ectodermal ridge (AER)-dependent expression of Sonic hedgehog (Shh), and AER-dependent zone of polarizing activity (ZPA) signaling. We also find that ectopi c FGF-2 applied to the posterior wing bud caused a dramatic change in the morphology of the limb bud, and results in limbs that display a re duction in the length of individual skeletal elements and loss of digi ts. Associated with these morphological changes was an FGF-2-stimulate d expansion and bifurcation of the expression domains of two posterior ly expressed genes, Shh and HoxD13. Applying FGF-2 at a central or ant erior location in the limb bud did not alter the Shh expression domain or cause digit loss. To test whether ectopic application of FGF-2 int o the posterior limb bud was influencing the movement of limb bud cell s, we used the lipophilic dye DiI to map the behavior of posterior cel ls in response to FGF-2. In response to FGF-2 posterior limb bud cells move in both a proximal and a distal direction, causing the initially labeled cell population to bifurcate into two distinct domains. Our d ata suggest that FGF-2 is influencing limb outgrowth by modifying cell movements and subsequent position-specific cell-cell interactions tha t are important for limb morphogenesis. (C) 1996 Wiley-Liss, Inc.