Developmental regulation of myosin gene expression in mouse cardiac muscle

Gary E. Lyons, Stefano Schiaffino, David Sassoon, Paul Barton, Margaret Buckingham

Research output: Contribution to journalArticlepeer-review

353 Scopus citations

Abstract

Expression of the two isoforms of cardiac myosin heavy chain (MHC), MHCα and MHCβ, in mammals is regulated postnatally by a variety of stimuli, including serum hormone levels. Less is known about the factors that regulate myosin gene expression in rapidly growing cardiac muscle in embryos. Using isoform-specific 35S-labeled cRNA probes corresponding to the two MHC genes and the two myosin alkali light chain (MLC) genes expressed in cardiac muscle, we have investigated the temporal and spatial pattern of expression of these different genes in the developing mouse heart by in situ hybridization. Between 7.5 and 8 d post coitum (p.c.), the newly formed cardiac tube begins to express MHCα, MHCα, MLC1 atrial (MLC1A), and MLC1 ventricular (MLC1V) gene transcripts at high levels throughout the myocardium. As a distinct ventricular chamber forms between 8 and 9 d p.c., MHCβ mRNAs begin to be restricted to ventricular myocytes. This process is complete by 10.5 d p.c. During this time, MHCα mRNA levels decrease in ventricular muscle cells but continue to be expressed at high levels in atrial muscle cells. MHCα transcripts continue to decrease in ventricular myocytes until 16 d p.c., when they are detectable at low levels, but then increase, and finally replace MHCβ mRNAs in ventricular muscle by 7 d after birth. Like MHCβ, MLC1V transcripts become restricted to ventricular myocytes, but at a slower rate. MLC1V mRNAs continue to be detected at low levels in atrial cells until 15.5 d p.c. MLC1A mRNA levels gradually decrease but are still detectable in ventricular cells until a few days after birth. This dynamic pattern of changes in the myosin phenotype in the prenatal mouse heart suggests that there are different regulatory mechanisms for cell-specific expression of myosin isoforms during cardiac development.

Original languageEnglish
Pages (from-to)2427-2436
Number of pages10
JournalJournal of Cell Biology
Volume111
Issue number6 PART 1
StatePublished - Dec 1990
Externally publishedYes

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