Developmental basis of limb length in rodents: evidence for multiple divisions of labor in mechanisms of endochondral bone growth

SUMMARY Mammals are remarkably diverse in limb lengths and proportions, but the number and kind of developmental mechanisms that contribute to length differences between limb bones remain largely unknown. Intra- and interspecific differences in bone length could result from variations in the cellular processes of endochondral bone growth, creating differences in rates of chondrocyte proliferation or hypertrophy, variation in the shape and size of chondrocytes, differences in the number of chondrocytes in precursor populations and throughout growth, or a combination of these mechanisms. To address these questions, this study compared cellular mechanisms of endochondral bone growth in cross-sectional ontogenetic series of the appendicular skeleton of two rodent species: the mouse ( Mus musculus ) and Mongolian gerbil ( Meriones unguiculatus ). Results indicate that multiple cellular processes of endochondral bone growth contribute to phenotypic differences in limb bone length. The data also suggest that separate developmental processes contribute to intraspecific length differences in proximal versus distal limb bones, and that these proximo-distal mechanisms are distinct from mechanisms that contribute to interspecific differences in limb bone length related to body size. These developmental "divisions of labor" are hypothesized to be important features of vertebrate limb development that allow (1) morphology in the autopods to evolve independently of the proximal limb skeleton, and (2) adaptive changes in limb proportions related to locomotion to evolve independently of evolutionary changes in body size.