|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.
|Source:||Development (Cambridge, England) 147(12): (Journal)|
|Registered Authors:||Galloway, Jenna|
|Keywords:||Chemical screen, Scleraxis, Statin, Tendon, Zebrafish|
|PubMed:||32467241 Full text @ Development|
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):.
ABSTRACTTendons 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.