TGF-β signaling is critical for maintenance of the tendon cell fate

Studies of cell fate focus on specification, but little is known about maintenance of the differentiated state. We find that TGF{beta} signaling plays an essential role in maintenance of the tendon cell fate. To examine the role TGF{beta} signaling in tenocytes TGF{beta} type II receptor was targeted in the Scleraxis cell lineage. Tendon development was not disrupted in mutant embryos, but shortly after birth tenocytes lost differentiation markers and reverted to a more stem/progenitor state. Targeting of Tgfbr2 using other Cre drivers did not cause tenocyte dedifferentiation suggesting a critical significance for the spatio-temporal activity of ScxCre. Viral reintroduction of Tgfbr2 to mutants was sufficient to prevent and even rescue mutant tenocytes suggesting a continuous and cell-autonomous role for TGF{beta} signaling in cell fate maintenance. These results uncover the critical importance of molecular pathways that maintain the differentiated cell fate and a key role for TGF{beta} signaling in these processes.