Making a heart: advances in understanding the mechanisms of cardiac development.

Purpose Of Review: The study of cardiac development is critical to inform management strategies for congenital and acquired heart disease. This review serves to highlight some of the advances in this field over the past year.

Recent Findings: Three main areas of study are included that have been particularly innovative and progressive.

Cardiac-specific deletion of the microtubule-binding protein CENP-F causes dilated cardiomyopathy.

CENP-F is a large multifunctional protein with demonstrated regulatory roles in cell proliferation, vesicular transport and cell shape through its association with the microtubule (MT) network. Until now, analysis of CENP-F has been limited to in vitro analysis. Here, using a Cre-loxP system, we report the in vivo disruption of CENP-F gene function in murine cardiomyocytes, a cell type displaying high levels of CENP-F expression.

CMF1-Rb interaction promotes myogenesis in avian skeletal myoblasts.

CMF1 protein is expressed in developing striated muscle before the expression of contractile proteins, and depletion of CMF1 in myoblasts results in inability to express muscle-specific proteins. Previous studies of CMF1 identify a functional Rb-binding domain, which is conserved in the murine and human homologues. Here, we show that CMF1 binds Rb family members, while a CMF1 protein with deletion of the Rb-binding domain (Rb-del CMF1) does not.

Specific deletion of CMF1 nuclear localization domain causes incomplete cell cycle withdrawal and impaired differentiation in avian skeletal myoblasts.

CMF1 is a protein expressed in embryonic striated muscle with onset of expression preceding that of contractile proteins. Disruption of CMF1 in myoblasts disrupts muscle-specific protein expression. Preliminary studies indicate both nuclear and cytoplasmic distribution of CMF1 protein, suggesting functional roles in both cellular compartments.

LEK1 protein expression in normal and dysregulated cardiomyocyte mitosis.

A defining characteristic of embryonic cells is their ability to divide rapidly, even in tissues such as cardiac muscle, which cannot divide once fully differentiated. This suggests that regulators of cell division differ in embryonic and differentiated cells. LEK1 is a member of an emerging family of proteins with diverse functions but shared structural domains, including numerous leucine zippers, a nuclear localization site, and a functional Rb-binding domain.

LEK1 is a potential inhibitor of pocket protein-mediated cellular processes.

LEK1, a member of the LEK family of proteins, is ubiquitously expressed in developing murine tissues. Our current studies are aimed at identifying the role of LEK1 during cell growth and differentiation. Little is known about the function of LEK proteins.

New frontiers in molecular pediatric cardiology.

Numerous advances in understanding the molecular basis of congenital heart disease have been published in the past year. Highlights are reviewed, focusing on two major topics: genetic syndromes and cardiac organogenesis. Genetic syndromes are discussed in the context of complementary data from targeted mutations in animals and genetic mapping studies in humans.