PUBLICATION

The mevalonate pathway is a critical regulator of tendon cell specification

Authors

Chen, J.W., Niu, X., King, M.J., Noedl, M.T., Tabin, C.J., Galloway, J.L.

ID

ZDB-PUB-200530-8

Date

2020

Source

Development (Cambridge, England) 147(12): (Journal)

Registered Authors

Galloway, Jenna

Keywords

Chemical screen, Scleraxis, Statin, Tendon, Zebrafish

MeSH Terms

SOX9 Transcription Factor/genetics
SOX9 Transcription Factor/metabolism
Signal Transduction
Morpholinos/metabolism
Neural Crest/metabolism
Stem Cells/cytology
Stem Cells/metabolism
Atorvastatin/pharmacology
Tendons/cytology
Tendons/metabolism*
Tendons/pathology
SOXE Transcription Factors/genetics
SOXE Transcription Factors/metabolism
Animals, Genetically Modified/metabolism
Cell Proliferation/drug effects
Cell Differentiation/drug effects
Mevalonic Acid/metabolism*
Zebrafish/metabolism
Farnesyltranstransferase/antagonists & inhibitors
Farnesyltranstransferase/genetics
Farnesyltranstransferase/metabolism
Alkyl and Aryl Transferases/antagonists & inhibitors
Alkyl and Aryl Transferases/genetics
Alkyl and Aryl Transferases/metabolism
Animals
rac GTP-Binding Proteins/antagonists & inhibitors
rac GTP-Binding Proteins/metabolism
Zebrafish Proteins/antagonists & inhibitors
Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism

(all 30)

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.

Genes / Markers

Figures