Using Normal Variation in Mouse Ossification to Identify Genes Underlying Growth Plate Formation

The great diversity in primate skeletal shape is in large part dictated by variation in growth rate. Longitudinal growth occurs at growth plates, which amplify and maintain the process of chondrocyte differentiation throughout ontogeny. Thanks to experiments in model organisms such as the mouse, knowledge of growth plate physiology has blossomed; yet, little is known about how growth plate location and behavior are patterned to produce the normal diversity in skeletal shapes. Fortunately, substantial anatomical variation exists within the mammalian skeleton that can be used to identify the mechanisms underlying growth plate formation. The pisiform (in non-human mammals) and calcaneus each form an active growth plate unlike the other carpals and tarsals, and the metatarsals form a growth plate at only one end. In each of these cases, growth plate containing tissues can be paired with tissues undergoing generalized endochondral ossication that control for the effects of age, systemic growth factors, and biomechanical environment. We performed global transcriptome sequencing (RNA-seq) on 0-, 4- and 9-day old mouse growth plate forming and non-forming tissues to identify growth plate-speciܪc genes. Signiܪcant differences in gene expression were detected with differentially expressed genes enriched in gene ontology categories associated with cartilage and skeletal development. Expression differences were also found in genes previously not known to have a role in skeletal development. Identication of the genes involved in the natural formation of mouse growth plates will aid our understanding of the mechanisms underlying differences in skeletal shape among primates.