ZFIN ID: ZDB-PUB-200530-8
The mevalonate pathway is a critical regulator of tendon cell specification
Chen, J.W., Niu, X., King, M.J., Noedl, M.T., Tabin, C.J., Galloway, J.L.
Date: 2020
Source: Development (Cambridge, England)   147(12): (Journal)
Registered Authors: Galloway, Jenna
Keywords: Chemical screen, Scleraxis, Statin, Tendon, Zebrafish
MeSH Terms:
  • 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
PubMed: 32467241 Full text @ Development
ABSTRACT
Tendons and ligaments are critical components of the musculoskeletal system, yet the pathways specifying this lineage 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 sox10+/sox9a+ skeletal lineage. The effect on tendon cell expansion is specific to the geranylgeranylation branch of the mevalonate pathway and 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.
ADDITIONAL INFORMATION