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Publication : HES factors regulate specific aspects of chondrogenesis and chondrocyte hypertrophy during cartilage development.

First Author  Rutkowski TP Year  2016
Journal  J Cell Sci Volume  129
Issue  11 Pages  2145-55
PubMed ID  27160681 Mgi Jnum  J:247121
Mgi Id  MGI:5922773 Doi  10.1242/jcs.181271
Citation  Rutkowski TP, et al. (2016) HES factors regulate specific aspects of chondrogenesis and chondrocyte hypertrophy during cartilage development. J Cell Sci 129(11):2145-55
abstractText  RBPjkappa-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 RBPjkappa-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.
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