Reference - Detail
|Author||Chen JW, Niu X, King MJ, Noedl MT, Tabin CJ, Galloway JL.|
|Title||The mevalonate pathway is a crucial regulator of tendon cell specification.|
Tendons and ligaments are crucial components of the musculoskeletal system, yet the pathways specifying these fates remain poorly defined. Through a screen of known bioactive chemicals in zebrafish, we identified a new pathway regulating tendon cell induction. We established that statin, through inhibition of the mevalonate pathway, causes an expansion of the tendon progenitor population. Co-expression and live imaging studies indicate that the expansion does not involve an increase in cell proliferation, but rather results from re-specification of cells from the neural crest-derived sox9a+/sox10+ skeletal lineage. The effect on tendon cell expansion is specific to the geranylgeranylation branch of the mevalonate pathway and is mediated by inhibition of Rac activity. This work establishes a novel role for the mevalonate pathway and Rac activity in regulating specification of the tendon lineage.
|MeSH||Alkyl and Aryl Transferases / antagonists & inhibitors Alkyl and Aryl Transferases / genetics Alkyl and Aryl Transferases / metabolism Animals Animals, Genetically Modified / metabolism Atorvastatin / pharmacology Cell Differentiation / drug effects Cell Proliferation / drug effects Farnesyltranstransferase / antagonists & inhibitors Farnesyltranstransferase / genetics Farnesyltranstransferase / metabolism Mevalonic Acid / metabolism* Morpholinos / metabolism Neural Crest / metabolism SOX9 Transcription Factor / genetics SOX9 Transcription Factor / metabolism SOXE Transcription Factors / genetics SOXE Transcription Factors / metabolism Signal Transduction Stem Cells / cytology Stem Cells / metabolism Tendons / cytology Tendons / metabolism* Tendons / pathology Zebrafish / metabolism Zebrafish Proteins / antagonists & inhibitors Zebrafish Proteins / genetics Zebrafish Proteins / metabolism rac GTP-Binding Proteins / antagonists & inhibitors rac GTP-Binding Proteins / metabolism|