The mechanisms by which Foxo proteins regulate metabolism are relatively well characterized. However, little was known about the mechanisms by which these same proteins regulate cellular differentiation.
New data generated by Domenico Accili and colleagues at Columbia University, New York, now indicates that Foxo1 cooperates with Notch to control muscle cell differentiation in vitro.
Overexpression of either a constitutively active form of Foxo1 or a constitutively active form of Notch was found to inhibit the in vitro differentiation of a mouse myoblast cell line.
Further analysis revealed that Foxo1 binds to the effector of Notch signaling Csl and that this is required for Notch activation of its target gene Hes1, which suppresses the expression of the myoblast differentiation factor MyoD. Consistent with this, mice lacking Foxo1 in skeletal muscle cells have more MyoD-containing muscle fibers.
The authors therefore suggest that Notch and Foxo1 cooperation might allow environmental and metabolic cues, respectively, to be integrated into the muscle cell differentiation decision.
Article: A Foxo/Notch pathway controls myogenic differentiation and fiber type specification
Materials provided by Journal of Clinical Investigation. Note: Content may be edited for style and length.
Cite This Page: