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Myosin is an essential component of cardiac muscle, from the onset of cardiogenesis through to the adult heart. Although traditionally known for its role in energy transduction and force development, recent studies suggest that both myosin heavy-chain and myosin light-chain proteins are required for a correctly formed heart. Myosins are structural proteins that are not only expressed from early stages of heart development, but when mutated in humans they may give rise to congenital heart defects. This review will discuss the roles of myosin, specifically with regards to the developing heart. The expression of each myosin protein will be described, and the effects that altering expression has on the heart in embryogenesis in different animal models will be discussed. The human molecular genetics of the myosins will also be reviewed. [ABSTRACT FROM AUTHOR]

Atrial septal defect is one of the most common forms of congenital heart malformation. We identified a new locus linked with atrial septal defect on chromosome 14q12 in a large family with dominantly inherited atrial septal defect. The underlying mutation is a missense substitution, I820N, ina-myosin heavy chain (MYH6), a structural protein expressed at high levels in the developing atria, which affects the binding of the heavy chain to its regulatory light chain. The cardiac transcription factor TBX5 strongly regulates expression of MYH6, but mutant forms of TBX5, which cause Holt-Oram syndrome, do not. Morpholino knock-down of expression of the chick MYH6 homolog eliminates the formation of the atrial septum without overtly affecting atrial chamber formation. These data provide evidence for a link between a transcription factor, a structural protein and congenital heart disease. [ABSTRACT FROM AUTHOR]

Human trisomy 18 (Edwards syndrome) provides a model for the role that genes on chromosome 18 play in fetal development. Trisomy 18 occurs in approximately 1 in 3000 live births. Despite its compatibility with life in 5% of cases, prolonged survival is rare. Anomalies involve the urogenital, cardiac, craniofacial and central nervous systems. The abnormalities could be caused by the abnormal expresion of developmentally important genes on chromosome 18. We have investigated the quantity and localisation of the expression of a candidate gene, transthyretin (TTR), on chromosome 18 at the RNA level in intestine and liver tissues from trisomic fetuses and have compared the expression with normal age-matched fetal tissues. The mRNA level of TTR in 10 to 14-week intestine was the same in trisomy 18 and control tissues. However, overexpression was seen for both trisomy 18 liver and intestine at 20-23 weeks. TTR transports both thyroxine and retinol and is therefore important for normal fetal development. [ABSTRACT FROM AUTHOR]