Limb Development and Regeneration

Experiments on developing and regenerating vertebrate limbshave led to the idea that pattern formation and growth controlare causally linked. The mechanism by which position-specificgrowth occurs is termed intercalation, and evidence is presentedthat implicates intercalation in the initiation, maintenanceand cessation of growth during limb formation. We conclude thatamong the variety of cell types present in limbs, only fibroblastshave been shown to possess the positional information necessaryfor intercalation. Hence we propose that the limb pattern isgenerated by intercalation between fibroblasts to give riseto a connective tissue scaffold, which in turn dictates thepositioning and morphogenesis of all of the differentiated celltypes of the limb. Finally, we review evidence that regenerativefailure among higher vertebrates is linked to defects in theintrinsic cellular mechanisms of growth control (intercalation)and conclude that progress towards the goal of stimulating regenerativelimb outgrowth in non-regenerating vertebrates will be contingentupon a better understanding of these intrinsic mechanisms.