The apical ectodermal ridge (AER) controls limb outgrowth and patterning, such that its removal causes changes in mesodermal gene expression, cell death and limb truncation. Fibroblast growth factor (FGF) family members are expressed in the AER and can rescue limb bud outgrowth after AER removal. Cells localized underneath the AER are maintained in an undifferentiated state by the FGFs produced by the AER. MAPK phosphatase 3 (mkp3) is a downstream effector of FGF8 signalling during limb bud development and is expressed in the distal limb mesenchyme. The present work evidences a gradient of mkp3 transcripts along the chick limb bud, in a distal to proximal direction. mkp3 transcription occurs only in the most distal limb bud cells and its mRNA gradient throughout the limb results from progressive rnRNA decay. We show that FGF8-soaked beads induce ectopic mkp3 expression, indicating that AER-derived FGF8 protein may activate mkp3 in the distal mesenchyme. (c) 2006 Elsevier Inc. All rights reserved.