Primary cilia are necessary for Prx1-expressing cells to contribute to postnatal skeletogenesis
Primary cilia are necessary for Prx1-expressing cells to contribute to postnatal skeletogenesis
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DOI：
10.1242/jcs.217828
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发表时间：
2018-08-01
影响因子：
4
通讯作者：
Jacobs, Christopher R.
中科院分区：
文献类型：
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作者：
Moore, Emily R.;Yang, Yuchen;Jacobs, Christopher R.
虽然Prx 1（也称为PRRX 1）表达细胞及其初级纤毛对胚胎发育至关重要，但由于小鼠模型的致死性，它们尚未在出生后骨骼发生的背景下进行研究。一个他莫昔芬诱导的Prx 1模型已经开发出来，我们确定，由这个启动子指导的表达是高度限制在出生后的骨膜和软骨膜形成层。为了确定这些形成层骨软骨祖细胞（CLOPs）及其初级纤毛的出生后作用，我们开发了跟踪CLOPs（Prx 1CreERGFP; Rosa 26 tdTomato）命运并选择性破坏其纤毛（Prx 1CreERGFP; Ift 88（fl/fl））的模型。我们的跟踪研究表明，CLOPs填充皮质骨和松质骨，生长板和次生骨化中心在正常程序的出生后骨骼发生。此外，缺乏CLOP纤毛的动物由于软骨内骨化和膜内骨化的破坏而表现出肢体发育迟缓。组织学检查表明，由于生长板中有限的分化、增殖和/或异常肥大分化，生长受到阻碍。总的来说，我们的研究结果表明，CLOPs被编程为通过出生后骨骼中的初级纤毛介导机制快速填充远端组织并产生骨骼。
Although Prx1 (also known as PRRX1)-expressing cells and their primary cilia are critical for embryonic development, they have yet to be studied in the context of postnatal skeletogenesis owing 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 (Prx1CreERGFP; Rosa26tdTomato) and selectively disrupt their cilia (Prx1CreERGFP; Ift88(fl/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 that 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 via a primary cilium-mediated mechanism in the postnatal skeleton.