1. The molecular complex of ciliary and golgin protein is crucial for skull development
- Author
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Lakmini Kumari Senavirathna, Hiroyuki Yamaguchi, Matthew D. Meyer, Sheng Pan, Li He, and Yoshihiro Komatsu
- Subjects
0301 basic medicine ,Proteomics ,Mutant ,Golgi Apparatus ,Endogeny ,Biology ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Calcification, Physiologic ,Osteogenesis ,medicine ,Animals ,Secretion ,Molecular Biology ,Process (anatomy) ,Cell Proliferation ,Mice, Knockout ,Osteoblasts ,Mesenchymal stem cell ,Skull ,Golgi Matrix Proteins ,Cell Differentiation ,Phenotype ,Cell biology ,Cytoskeletal Proteins ,030104 developmental biology ,medicine.anatomical_structure ,Neural Crest ,Intramembranous ossification ,Collagen ,Carrier Proteins ,030217 neurology & neurosurgery ,Developmental Biology ,Research Article - Abstract
Intramembranous ossification, which consists of direct conversion of mesenchymal cells to osteoblasts, is a characteristic process in skull development. One critical role of these osteoblasts is to secrete collagen-containing bone matrix. However, it remains unclear how the dynamics of collagen trafficking is regulated during skull development. Here, we reveal the regulatory mechanisms of ciliary and golgin proteins required for intramembranous ossification. During normal skull formation, osteoblasts residing on the osteogenic front actively secreted collagen. Mass spectrometry and proteomic analysis determined endogenous binding between ciliary protein IFT20 and golgin protein GMAP210 in these osteoblasts. Like in Ift20 mutant mice, disruption of neural-crest specific GMAP210 in mice caused osteopenia-like phenotypes due to dysfunctional collagen trafficking. Mice lacking both IFT20 and GMAP210 displayed more severe skull defects compared to either IFT20 or GMAP210 mutants. These results demonstrate that the molecular complex of IFT20 and GMAP210 is essential for the intramembranous ossification during skull development.
- Published
- 2021