DYNAMIC LEFT RIGHT REGIONALIZATION OF ENDOGENOUS MYOSIN LIGHT-CHAIN 3F TRANSCRIPTS IN THE DEVELOPING MOUSE HEART/

It has recently emerged that transcriptional differences exist between left and right cardiac chambers. An example is provided by transgenic mice with an nlacZ reporter gene under transcriptional control of the fast slteletal muscle alkali myosin light chain (MLC) 3 promoter and 3' enhancer, which express beta-galactosidase in a left ventricular-ri ght atrial dominant pattern in the developing and adult heart, Here, w e demonstrate that endogenous MLC3F transcripts are also left/right re gionalised in the mouse heart during embryonic development. Regionalis ation is observed as early as embryonic day (E) 8.5, and by E10.5 MLC3 F transcripts are present predominantly in the future left ventricle a nd right atrium, and to a lesser extent in the left atrium, Subsequent ly, MLC3F transcripts are down-regulated in the left ventricle, and by E12.5 expression is restricted to both atria and left-ventricular tra beculae. No MLC3F protein can be detected in the adult or embryonic mo use heart, suggesting that post-transcriptional regulation prevents th is fast myosin isoform contributing to myocardial contraction. Left ve ntricular-right atrial dominant MLC3F transgenes therefore reflect tra nsitory left/right regionalisation of the endogenous gene, unlike othe r reported cases of transgene regionalisation. MLC3F transgenes, howev er, maintain an embryonic-like distribution throughout development sug gesting that myocardial gene expression is controlled by distinct temp oral, as well as spatial, regulatory module. (C) 1998 Academic Press.