Suppression of atrial myosin gene expression occurs independently in the left and right ventricles of the developing mouse heart

Many cardiac genes are broadly expressed in the early heart and become rest ricted to the atria or ventricles as development proceeds, Additional trans criptional differences between left and right compartments of the embryonic heart have been described recently, in particular for a number of transgen es containing cardiac regulatory elements. We now demonstrate that three my osin genes which become transcriptionally restricted to the atria between e mbryonic day (E) 12.5 and birth, alpha-myosin heavy chain (MHC), myosin lig ht chain (MLC) 1A and MLC2A, are coordinately downregulated in the compact myocardium of the left ventricle before that of the right ventricle, alpha- MHC protein also accumulates in the right, but not left, compact ventricula r myocardium during this period, suggesting that this transient regionalisa tion contributes to foetal heart function. dHAND and eHAND, basic helix-loo p-helix transcription factors known to be expressed in the right and left v entricles respectively at E10.5, remain regionalised between E12.5 and E14. 5, Downregulation of alpha-MHC, MLC1A, and MLC2A in iv/iv embryos, which ha ve defective left/right patterning, initiates in the morphological left (sy stemic) ventricle regardless of its anatomical position on the right or lef t hand side of the heart. This points to the importance of left/right ventr icular differences in sarcomeric gene expression patterns during foetal car diogenesis and indicates that these differences originate in the embryo in response to anterior-posterior patterning of the heart tube rather than as a result of cardiac looping. (C) 2000 Wiley-Liss, Inc.