Sharp-1 regulates TGF-β signaling and skeletal muscle regeneration.

Sharp-1 is a basic helix-loop-helix (bHLH) transcriptional repressor that is involved in a number of cellular processes. Our previous studies have demonstrated that Sharp-1 is a negative regulator of skeletal myogenesis and it blocks differentiation of muscle precursor cells by modulating the activity of MyoD. In order to understand its role in pre- and post-natal myogenesis, we assessed skeletal muscle development and freeze-injury-induced regeneration in Sharp-1-deficient mice.

SHARP1/DEC2 inhibits adipogenic differentiation by regulating the activity of C/EBP.

SHARP1, a basic helix-loop-helix transcription factor, is expressed in many cell types; however, the mechanisms by which it regulates cellular differentiation remain largely unknown. Here, we show that SHARP1 negatively regulates adipogenesis. Although expression of the early marker CCAAT/enhancer binding protein beta (C/EBPbeta) is not altered, its crucial downstream targets C/EBPalpha and peroxisome proliferator-activated receptor gamma (PPARgamma) are downregulated by SHARP1.

Analysis of growth properties and cell cycle regulation using mouse embryonic fibroblast cells.

A balance between proliferation and apoptosis is crucial for cellular homeostasis, and its disruption leading to enhanced cellular proliferation and uncontrolled growth are hallmarks of cancer. Genetic manipulation in the mouse offers a powerful approach to delineate the roles of genes in carcinogenesis and determine the molecular and cellular basis of their function. Mouse embryonic fibroblast cells derived from mice that are disrupted for tumor suppressors or oncogenes have served as an invaluable tool to study altered growth properties of cells and identify regulatory molecules involved in neoplastic transformation.

Stra13 regulates satellite cell activation by antagonizing Notch signaling.

Satellite cells play a critical role in skeletal muscle regeneration in response to injury. Notch signaling is vital for satellite cell activation and myogenic precursor cell expansion but inhibits myogenic differentiation. Thus, precise spatial and temporal regulation of Notch activity is necessary for efficient muscle regeneration.