ArticleProceedings of the National Academy of Sciences of the United States of America2016
Canonical and noncanonical intraflagellar transport regulates craniofacial skeletal development.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 79 citations in OpenAlex.
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- Ciliary-Mediated Mechanotransduction in Skeletal Development and Diseases.Results and problems in cell differentiation · 2026Review
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- Disruption of distal appendage protein CEP164 causes skeletal malformation in mice.Biochemical and biophysical research communications · 2024Article
- A loss of primary cilia by a reduction in mTOR signaling correlates with age-related deteriorations in condylar cartilage.GeroScience · 2024Article
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- Skeletal ciliopathy: pathogenesis and related signaling pathways.Molecular and cellular biochemistry · 2024Review
- IFT20 and WWTR1 govern bone homeostasis via synchronously regulating the expression and stability of TβRII in osteoblast lineage cells.Research square · 2024Article
- Enhanced BMP signaling in Cathepsin K-positive tendon progenitors induces heterotopic ossification.Biochemical and biophysical research communications · 2023Article
- Deletion of IFT20 exclusively in the RPE ablates primary cilia and leads to retinal degeneration.PLoS biology · 2023Article
- Review
- Hedgehog-Related Mutation Causes Bone Malformations with or without Hereditary Gene Mutations.International journal of molecular sciences · 2023Review
- Regulation of c-SMAC formation and AKT-mTOR signaling by the TSG101-IFT20 axis in CD4Cellular & molecular immunology · 2023Article
- The factory, the antenna and the scaffold: the three-way interplay between the Golgi, cilium and extracellular matrix underlying tissue function.Biology open · 2023Review
- Protection of primary cilia is an effective countermeasure against the impairment of osteoblast function induced by simulated microgravity.Journal of cellular and molecular medicine · 2023Article
- Primary Cilia: The New Face of Craniofacial Research.Biomolecules · 2022Review
- IFT20: An Eclectic Regulator of Cellular Processes beyond Intraflagellar Transport.International journal of molecular sciences · 2022Review
- Disruption of Trip11 in cranial neural crest cells is associated with increased ER and Golgi stress contributing to skull defects in mice.Developmental dynamics : an official publication of the American Association of Anatomists · 2022Article
- NGF-p75 signaling coordinates skeletal cell migration during bone repair.Science advances · 2022Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The primary cilium is a cellular organelle that coordinates signaling pathways critical for cell proliferation, differentiation, survival, and homeostasis. Intraflagellar transport (IFT) plays a pivotal role in assembling primary cilia. Disruption and/or dysfunction of IFT components can cause multiple diseases, including skeletal dysplasia. However, the mechanism by which IFT regulates skeletogenesis remains elusive. Here, we show that a neural crest-specific deletion of intraflagellar transport 20 (Ift20) in mice compromises ciliogenesis and intracellular transport of collagen, which leads to osteopenia in the facial region. Whereas platelet-derived growth factor receptor alpha (PDGFRα) was present on the surface of primary cilia in wild-type osteoblasts, disruption of Ift20 down-regulated PDGFRα production, which caused suppression of PDGF-Akt signaling, resulting in decreased osteogenic proliferation and increased cell death. Although osteogenic differentiation in cranial neural crest (CNC)-derived cells occurred normally in Ift20-mutant cells, the process of mineralization was severely attenuated due to delayed secretion of type I collagen. In control osteoblasts, procollagen was easily transported from the endoplasmic reticulum (ER) to the Golgi apparatus. By contrast, despite having similar levels of collagen type 1 alpha 1 (Col1a1) expression, Ift20 mutants did not secrete procollagen because of dysfunctional ER-to-Golgi trafficking. These data suggest that in the multipotent stem cells of CNCs, IFT20 is indispensable for regulating not only ciliogenesis but also collagen intracellular trafficking. Our study introduces a unique perspective on the canonical and noncanonical functions of IFT20 in craniofacial skeletal development.
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