Primary cilia are necessary for Prx1-expressing cells to contribute to postnatal skeletogenesis

Abstract

Although Prx1-expressing cells and their primary cilia are critical for embryonic development, they have yet to be studied in the context of postnatal skeletogenesis due to the lethality of mouse models. A tamoxifen-inducible Prx1 model has been developed and we determined that expression directed by this promoter is highly restricted to the cambium layers in the periosteum and perichondrium after birth. To determine the postnatal role of these cambium layer osteochondroprogenitors (CLOPs) and their primary cilia, we developed models to track the fate of CLOPs (Prx1CreER-GFP; Rosa26tdTomato) and selectively disrupt their cilia (Prx1CreER-GFP; Ift88fl/fl). Our tracking studies revealed that CLOPs populate cortical and trabecular bone, the growth plate, and secondary ossification centers during the normal program of postnatal skeletogenesis. Furthermore, animals lacking CLOP cilia exhibit stunted limb growth due to disruptions in endochondral and intramembranous ossification. Histological examination indicates growth is stunted due to limited differentiation, proliferation, and/ or abnormal hypertrophic differentiation in the growth plate. Collectively, our results suggest that CLOPs are programmed to rapidly populate distant tissues and produce bone in a primary cilium-mediated mechanism in the postnatal skeleton.