Making a ‘short bone’ short: Human pisiform reduction results from the loss of a growth plate

The wrist is fundamental to reconstructing hominoid phylogeny and behavior but limited understanding of the relative contributions that genetics verses remodeling play in determining skeletal form hinders these analyses. The human pisiform is a small, nodular bone. However, in most other mammals, including apes and likely Australopithecus afarensis, pisiforms are elongate and form from two ossification centers. We hypothesize that 1) the presence of a secondary center in mammalian pisiforms indicates the existence of a growth plate and 2) human pisiform reduction results from growth plate loss. To address these hypotheses, we first conducted a survey of hominoid pisiform ossification that confirms the presence of secondary ossification centers in all extant apes. Identification of the initial ossification center occurs substantially earlier in apes relative to humans, raising questions concerning homology of the human pisiform and the two mammalian ossification centers. Second, we conducted histological and immunohistochemical analyses of pisiform ossification and gene expression in juvenile mice. We confirm the presence of two ossification centers in mice separated by a cartilaginous growth plate. Growth plate marker expression localized appropriately to distinctly organized columnar (PCNA) and hypertrophic (Collagen X) chondrocyte zones. In addition, reduction of Hoxa11 and Hoxd11 results in pisiform shortening similar to humans, raising the possibility that human pisiform growth plate loss may be attributable to altered Hox expression. Thus, examination of pisiform reduction can serve as an entry point to better understand the patterning of hominoid wrist evolution and development.