Building Muscle Requires Foxo1

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Building Muscle Requires Foxo1

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.