Hoxd11 influences growth plate organization in the mammalian Pisi-form

The typical mammalian pisi-form is rod-shaped, forms from two centers of ossification, and contains an organized growth plate at the palmar end. The pisiform is the only carpal to form a growth plate; however, humans possess a short pisiform that forms from a single ossification center and lacks a growth plate. In the mouse, Hoxa11 and Hoxd11 mutations lead to abnormal shortening of this bone, and variable fusion between bones in the proximal carpal row. We have previously observed that Hoxd11 expression is present in tissues surrounding the developing pisiform in embryonic mice. This study seeks to examine the structure of shortened pisiforms in Hoxd11 mutant mice during development and determine if the growth plate is affected by deletion of one or both Hoxd11 alleles. We conducted histological analyses of the carpus in juvenile mice, comparing wild type (+/+) to heterozygotes (+/-) and homozygotes (-/-) for a Hoxd11 deletion. Pisiforms from +/+ and +/- mice have organized resting, columnar, and hypertrophic cartilaginous zones, while -/- mice have disorganized cartilage where the growth plate typically forms. We also observe fusion of the pisiform and triquetral in -/- mice, consistent with observations in previous studies. These results support the role of Hox genes in growth plate specification, and indicate that presence of Hoxd11 expression around the developing pisiform may signal formation of its growth plate. Additionally, these data may help to explain the developmental processes underlying evolutionary differences within the piso-triquetral complex among apes and humans, including the loss of a growth plate and substantial shortening of the human pisiform.