Sox6 is required for normal fiber type differentiation of fetal skeletal muscle in mice
Article first published online: 21 JUN 2007
Copyright © 2007 Wiley-Liss, Inc.
Volume 236, Issue 8, pages 2062–2076, August 2007
How to Cite
Hagiwara, N., Yeh, M. and Liu, A. (2007), Sox6 is required for normal fiber type differentiation of fetal skeletal muscle in mice. Dev. Dyn., 236: 2062–2076. doi: 10.1002/dvdy.21223
- Issue published online: 25 JUL 2007
- Article first published online: 21 JUN 2007
- Manuscript Accepted: 7 MAY 2007
- American Heart Association. Grant Number: Beginning Grant in Aid 0365010Y
- March of Dimes Birth Defects Foundation. Grant Number: Basil O'Connor Starter Scholar Research Award
- fetal skeletal muscle;
- muscle fiber types;
- terminal differentiation;
Sox6, a member of the Sox family of transcription factors, is highly expressed in skeletal muscle. Despite its abundant expression, the role of Sox6 in muscle development is not well understood. We hypothesize that, in fetal muscle, Sox6 functions as a repressor of slow fiber type-specific genes. In the wild-type mouse, differentiation of fast and slow fibers becomes apparent during late fetal stages (after approximately embryonic day 16). However, in the Sox6 null-p100H mutant mouse, all fetal muscle fibers maintain slow fiber characteristics, as evidenced by expression of the slow myosin heavy chain MyHC-β. Knockdown of Sox6 expression in wild-type myotubes results in a significant increase in MyHC-β expression, supporting our hypothesis. Analysis of the MyHC-β promoter revealed a Sox consensus sequence that likely functions as a negative cis-regulatory element. Together, our results suggest that Sox6 plays a critical role in the fiber type differentiation of fetal skeletal muscle. Developmental Dynamics 236:2062–2076, 2007. © 2007 Wiley-Liss, Inc.