Comparative analysis of mouse metatarsal ossification and implications for differential skeletal growth

RENO, P.L.*; MCBURNEY, D.L.; LOVEJOY, C.O.; HORTON, W.E.; Kent State University, OH; NEOUCOM, Rootstown, OH; Kent State University, OH; NEOUCOM, Rootstown, OH; Kent State University, OH; NEOUCOM, Rootstown, OH: Comparative analysis of mouse metatarsal ossification and implications for differential skeletal growth

The diversity of skeletal proportions in mammals is largely achieved by modifying physeal growth rate, yet little is known about how growth plate location and growth rate are specified. Like those of most mammals including humans, mouse metatarsals have only a single growth plate. These constitute an excellent model for exploring mechanisms that may underlie growth plate formation and for uncovering potential targets of natural selection for modifying longitudinal growth. Neonatal to 14 day old mice metatarsals were stained with Safranin O or monitored for protein expression via immunohistochemistry. While initially similar, the two ends diverged substantially with respect to the organization and size of their columnar and hypertrophic zones. PCNA expression revealed that a specific proliferation profile is associated with growth plate formation. Surprisingly, the expression of both PTHrP and its receptor are similar in both ends of the metatarsal, suggesting that these play a very general role in regulating endochondral ossification. In contrast, the expression patterns of PTC are distinct, suggesting that Ihh signaling may contribute to the determination of growth plate formation and performance. In addition, these patterns may also underlie the acquisition of novel growth centers in mammals. Comparison of mouse metatarsal ossification patterns to those of alligators revealed that the unidirectional pattern of metapodial growth (i.e., via a single growth plate) is derived in mammals. Comparisons of ossification within different skeletal regions and between divergent vertebrate taxa will therefore be useful in advancing our understanding of the development and evolution of the tetrapod skeleton.

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