HES factors regulate specific aspects of chondrogenesis and chondrocyte hypertrophy during cartilage development
| Autor: | Anat Kohn, Timothy P. Rutkowski, Matthew J. Hilton, Yinshi Ren, Anthony J. Mirando, Deepika Sharma |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Transcription Genetic HES5 Notch signaling pathway Chondrocyte hypertrophy Biology Mice 03 medical and health sciences Chondrocytes Internal medicine Genetic model Basic Helix-Loop-Helix Transcription Factors medicine Animals SOX9 Transcription Factor HES1 Molecular Biology Transcription factor Cell Proliferation Bone Development Cartilage Gene Expression Regulation Developmental Cell Differentiation Mesenchymal Stem Cells Hypertrophy Cell Biology Chondrogenesis Cell biology Repressor Proteins medicine.anatomical_structure 030104 developmental biology Endocrinology Hes3 signaling axis Transcription Factor HES-1 Developmental Biology Research Article |
| Zdroj: | Journal of Cell Science. |
| ISSN: | 1477-9137 0021-9533 |
| DOI: | 10.1242/jcs.181271 |
| Popis: | RBPjκ-dependent Notch signaling regulates multiple processes during cartilage development, including chondrogenesis, chondrocyte hypertrophy and cartilage matrix catabolism. Select members of the HES- and HEY-families of transcription factors are recognized Notch signaling targets that mediate specific aspects of Notch function during development. However, whether particular HES and HEY factors play any role(s) in the processes during cartilage development is unknown. Here, for the first time, we have developed unique in vivo genetic models and in vitro approaches demonstrating that the RBPjκ-dependent Notch targets HES1 and HES5 suppress chondrogenesis and promote the onset of chondrocyte hypertrophy. HES1 and HES5 might have some overlapping function in these processes, although only HES5 directly regulates Sox9 transcription to coordinate cartilage development. HEY1 and HEYL play no discernable role in regulating chondrogenesis or chondrocyte hypertrophy, whereas none of the HES or HEY factors appear to mediate Notch regulation of cartilage matrix catabolism. This work identifies important candidates that might function as downstream mediators of Notch signaling both during normal skeletal development and in Notch-related skeletal disorders. |
| Databáze: | OpenAIRE |
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