The MLC-2 Paradigm for Ventricular Heart Chamber Specification, Maturation, and Morphogenesis

Publisher Summary This chapter focuses on the molecular paradigms that illustrate how the expression of two isoforms of the regulatory or phosphorylable MLC-2 proteins, namely, the cardiac ventricular/slow twitch isoform (MLC-2v) and the cardiac atrial isoform (MLC-2a), is controlled. In addition, the unique role of MLC-2v in cardiac contractile function will be discussed in the context of the other myosin light chain isoforms. In studies using an in vitro model of cardiogenesis in embryonic stem (ES) cells, MLC-2v expression is found to occur independently of heart tube formation, suggesting that ventricular specification occurs relatively early in mammalian cardiogenesis. Comparison of MLC-2a and MLC-2v transcripts during cardiogenesis in differentiating ES cells revealed that MLC-2a is expressed in embryoid bodies as early as Day 6 compared to Day 9 for MLC-2v . Thus, MLC-2a and MLC-2v serve as genetic markers for atrial and ventricular chamber specification in both in vitro and in vivo contexts. The MLC-2v gene has been used as a model system to identify the molecular pathways that may play a role in ventricular chamber specification, maturation, and morphogenesis. The regulatory elements within the MLC-2v promoter, which confer ventricular specificity have been identified, as have several of the transcription factors that occupy these sites and form a combinatorial pathway for regulation of the ventricular muscle gene program.