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4096701 
Journal Article 
Enhanced BMP signaling prevents degeneration and leads to endochondral ossification of Meckel's cartilage in mice 
Wang, Y; Zheng, Y; Chen, D; Chen, Y 
2013 
Yes 
Developmental Biology
ISSN: 0012-1606
EISSN: 1095-564X 
381 
2 
301-311 
English 
23891934 
Meckel's cartilage is a transient supporting tissue of the embryonic mandible in mammals, and disappears by taking different ultimate cell fate along the distal-proximal axis, with the majority (middle portion) undergoing degeneration and chondroclastic resorption. While a number of factors have been implicated in the degeneration and resorption processes, signaling pathways that trigger this degradation are currently unknown. BMP signaling has been implicated in almost every step of chondrogenesis. In this study, we used Noggin mutant mice as a model for gain-of-BMP signaling function to investigate the function of BMP signaling in Meckel's cartilage development, with a focus on the middle portion. We showed that Bmp2 and Bmp7 are expressed in early developing Meckels' cartilage, but their expression disappears thereafter. In contrast, Noggin is expressed constantly in Meckel's cartilage throughout the entire gestation period. In the absence of Noggin, Meckel's cartilage is significantly thickened attributing to dramatically elevated cell proliferation rate associated with enhanced phosphorylated Smad1/5/8 expression. Interestingly, instead of taking a degeneration fate, the middle portion of Meckel's cartilage in Noggin mutants undergoes chondrogenic differentiation and endochondral ossification contributing to the forming mandible. Chondrocyte-specific expression of a constitutively active form of BMPRIa but not BMPRIb leads to enlargement of Meckel's cartilage, phenocopying the consequence of Noggin deficiency. Our results demonstrate that elevated BMP signaling prevents degeneration and leads to endochondral ossification of Meckel's cartilage, and support the idea that withdrawal of BMP signaling is required for normal Meckel's cartilage development and ultimate cell fate.