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
-
- SOXE Transcription Factors/genetics
- SOXE Transcription Factors/metabolism
- Morpholinos/metabolism
- Cell Differentiation/drug effects
- Alkyl and Aryl Transferases/antagonists & inhibitors
- Alkyl and Aryl Transferases/genetics
- Alkyl and Aryl Transferases/metabolism
- Animals
- Stem Cells/cytology
- Stem Cells/metabolism
- rac GTP-Binding Proteins/antagonists & inhibitors
- rac GTP-Binding Proteins/metabolism
- SOX9 Transcription Factor/genetics
- SOX9 Transcription Factor/metabolism
- Zebrafish/metabolism
- Atorvastatin/pharmacology
- Cell Proliferation/drug effects
- Farnesyltranstransferase/antagonists & inhibitors
- Farnesyltranstransferase/genetics
- Farnesyltranstransferase/metabolism
- Signal Transduction
- Tendons/cytology
- Tendons/metabolism*
- Tendons/pathology
- Mevalonic Acid/metabolism*
- Animals, Genetically Modified/metabolism
- Neural Crest/metabolism
- Zebrafish Proteins/antagonists & inhibitors
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 32467241 Full text @ Development
Citation
Chen, J.W., Niu, X., King, M.J., Noedl, M.T., Tabin, C.J., Galloway, J.L. (2020) The mevalonate pathway is a critical regulator of tendon cell specification. Development (Cambridge, England). 147(12):.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping