Which region of the limb bud is responsible for growth along the proximal-distal axis?
Growth along proximal-distal axis relies on progress zone, a highly mitotically active undifferentiated mesenchyme subjacent to apical ridge maintained by fibroblast growth factor 8 signaling. Cells residing longer in progress zone receive prolonged FGF exposure and adopt more distal fates: early exit yields stylopod humerus-femur, intermediate zeugopod radius-ulna-tibia-fibula, late retention autopod hand-foot. This progressive fate model explains sequential segment formation coordinated by Hox timing. Zone of polarizing activity patterns anterior-posterior axis, AER is signaling source, somites supply muscle progenitors for coordinated outgrowth.
Ref: Gilbert, Developmental Biology, 12th ed., Chapter 19: Progress zone model and proximal-distal limb outgrowth timing.