Myocardin--not quite MyoD.

Abstract

Smooth muscle cells (SMCs) have evolved to subserve a variety of diverse functions in higher vertebrates, including modulation of arterial tone, regulation of airway resistance, and control of gastrointestinal motility. The diverse functional capacities of SMCs are ultimately determined by the expression of genes encoding SMC-restricted contractile and cytoskeletal proteins, intracellular enzymes, cell surface ligands, and receptors. Several features distinguish the SMC lineage from the skeletal (fast and slow) and cardiac muscle cell lineages. In contrast to skeletal and cardiac muscle cells, SMCs fail to undergo terminal differentiation and permanently exit the cell cycle. In addition, SMCs retain the capacity to reversibly modulate their phenotype during postnatal development in response to a variety of extracellular stimuli including vessel wall injury. As such, the molecular programs underlying SMC differentiation must differ fundamentally from those programs governing skeletal and cardiac myocyte differentiation. See page 1596 Relatively little is currently understood about the molecular mechanisms that regulate SMC lineage specification, differentiation, and modulation of SMC phenotype. This is because, in part, of the complex embryological origins of the SMC lineage, which are derived both from mesodermally-derived lateral mesenchyme as well as ectodermally-derived neural crest. In addition, in contrast to skeletal and cardiac lineages, relatively few definitive markers of the SMC lineage have been identified, and expression of these markers may be undetectable when SMCs modulate their phenotype from contractile to synthetic (for review see Owens1). SM-myosin heavy chain (SMyHC) is generally considered the “definitive” SMC marker because it is expressed exclusively in SMCs and is not expressed in embryonic skeletal or cardiac muscle.2 Other SMC markers including SM-α-actin, calponin-h1, and SM22α are expressed predominantly in SMCs during postnatal development, but they are also transiently expressed in embryonic cardiac and/or skeletal myocytes (and/or other cell lineages).1 Each of these SMC markers …