Barx homeobox family in muscle development and regeneration

Abstract

Homeobox transcription factors are key intrinsic regulators of myogenesis. In studies spanning several years, we have characterized the homeobox factor Barx2 as a novel marker for muscle progenitor cells and an important regulator of muscle growth and repair. In this review, we place the expression and function of Barx2 and its paralogue Barx1 in context with other muscle-expressed homeobox factors in both embryonic and adult myogenesis. We also describe the structure and regulation of Barx genes and possible gene/disease associations. The functional domains of Barx proteins, their molecular interactions, and cellular functions are presented with particular emphasis on control of genes and processes involved in myogenic differentiation. Finally, we describe the patterns of Barx gene expression in vivo and the phenotypes of various Barx gene perturbation models including null mice. We focus on the Barx2 null mouse model, which has demonstrated the critical roles of Barx2 in postnatal myogenesis including muscle maintenance during aging, and regeneration of acute and chronic muscle injury.