Logo of jcellbiolHomeThe Rockefeller University PressEditorsContactInstructions for AuthorsThis issue
J Cell Biol. 1990 Dec 1; 111(6): 2427–2436.
PMCID: PMC2116419

Developmental regulation of myosin gene expression in mouse cardiac muscle


Expression of the two isoforms of cardiac myosin heavy chain (MHC), MHC alpha and MHC beta, 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 MHC alpha, MHC beta, 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., MHC beta mRNAs begin to be restricted to ventricular myocytes. This process is complete by 10.5 d p.c. During this time, MHC alpha mRNA levels decrease in ventricular muscle cells but continue to be expressed at high levels in atrial muscle cells. MHC alpha 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 MHC beta mRNAs in ventricular muscle by 7 d after birth. Like MHC beta, 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.

Full Text

The Full Text of this article is available as a PDF (4.2M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Bárány M. ATPase activity of myosin correlated with speed of muscle shortening. J Gen Physiol. 1967 Jul;50(6 Suppl):197–218. [PMC free article] [PubMed]
  • Barton PJ, Buckingham ME. The myosin alkali light chain proteins and their genes. Biochem J. 1985 Oct 15;231(2):249–261. [PMC free article] [PubMed]
  • Barton PJ, Cohen A, Robert B, Fiszman MY, Bonhomme F, Guénet JL, Leader DP, Buckingham ME. The myosin alkali light chains of mouse ventricular and slow skeletal muscle are indistinguishable and are encoded by the same gene. J Biol Chem. 1985 Jul 15;260(14):8578–8584. [PubMed]
  • Barton PJ, Robert B, Cohen A, Garner I, Sassoon D, Weydert A, Buckingham ME. Structure and sequence of the myosin alkali light chain gene expressed in adult cardiac atria and fetal striated muscle. J Biol Chem. 1988 Sep 5;263(25):12669–12676. [PubMed]
  • Braun T, Buschhausen-Denker G, Bober E, Tannich E, Arnold HH. A novel human muscle factor related to but distinct from MyoD1 induces myogenic conversion in 10T1/2 fibroblasts. EMBO J. 1989 Mar;8(3):701–709. [PMC free article] [PubMed]
  • Braun T, Bober E, Winter B, Rosenthal N, Arnold HH. Myf-6, a new member of the human gene family of myogenic determination factors: evidence for a gene cluster on chromosome 12. EMBO J. 1990 Mar;9(3):821–831. [PMC free article] [PubMed]
  • Chizzonite RA, Zak R. Regulation of myosin isoenzyme composition in fetal and neonatal rat ventricle by endogenous thyroid hormones. J Biol Chem. 1984 Oct 25;259(20):12628–12632. [PubMed]
  • Cummins P. Transitions in human atrial and ventricular myosin light-chain isoenzymes in response to cardiac-pressure-overload-induced hypertrophy. Biochem J. 1982 Jul 1;205(1):195–204. [PMC free article] [PubMed]
  • Cummins P, Lambert SJ. Myosin transitions in the bovine and human heart. A developmental and anatomical study of heavy and light chain subunits in the atrium and ventricle. Circ Res. 1986 Jun;58(6):846–858. [PubMed]
  • Davis RL, Weintraub H, Lassar AB. Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell. 1987 Dec 24;51(6):987–1000. [PubMed]
  • Dechesne CA, Leger JO, Leger JJ. Distribution of alpha- and beta-myosin heavy chains in the ventricular fibers of the postnatal developing rat. Dev Biol. 1987 Sep;123(1):169–178. [PubMed]
  • de Groot IJ, Lamers WH, Moorman AF. Isomyosin expression patterns during rat heart morphogenesis: an immunohistochemical study. Anat Rec. 1989 Jul;224(3):365–373. [PubMed]
  • de Jong F, Geerts WJ, Lamers WH, Los JA, Moorman AF. Isomyosin expression patterns in tubular stages of chicken heart development: a 3-D immunohistochemical analysis. Anat Embryol (Berl) 1987;177(1):81–90. [PubMed]
  • Gambke B, Lyons GE, Haselgrove J, Kelly AM, Rubinstein NA. Thyroidal and neural control of myosin transitions during development of rat fast and slow muscles. FEBS Lett. 1983 Jun 13;156(2):335–339. [PubMed]
  • Glass CK, Lipkin SM, Devary OV, Rosenfeld MG. Positive and negative regulation of gene transcription by a retinoic acid-thyroid hormone receptor heterodimer. Cell. 1989 Nov 17;59(4):697–708. [PubMed]
  • Gorza L, Saggin L, Sartore S, Ausoni S. An embryonic-like myosin heavy chain is transiently expressed in nodal conduction tissue of the rat heart. J Mol Cell Cardiol. 1988 Oct;20(10):931–941. [PubMed]
  • Ingwall JS, Kramer MF, Fifer MA, Lorell BH, Shemin R, Grossman W, Allen PD. The creatine kinase system in normal and diseased human myocardium. N Engl J Med. 1985 Oct 24;313(17):1050–1054. [PubMed]
  • Izumo S, Lompré AM, Matsuoka R, Koren G, Schwartz K, Nadal-Ginard B, Mahdavi V. Myosin heavy chain messenger RNA and protein isoform transitions during cardiac hypertrophy. Interaction between hemodynamic and thyroid hormone-induced signals. J Clin Invest. 1987 Mar;79(3):970–977. [PMC free article] [PubMed]
  • Kramer AW, Jr, Marks LS. The occurrence of cardiac muscle in the pulmonary veins of Rodenita. J Morphol. 1965 Sep;117(2):135–149. [PubMed]
  • Kurabayashi M, Komuro I, Tsuchimochi H, Takaku F, Yazaki Y. Molecular cloning and characterization of human atrial and ventricular myosin alkali light chain cDNA clones. J Biol Chem. 1988 Sep 25;263(27):13930–13936. [PubMed]
  • Lompré AM, Nadal-Ginard B, Mahdavi V. Expression of the cardiac ventricular alpha- and beta-myosin heavy chain genes is developmentally and hormonally regulated. J Biol Chem. 1984 May 25;259(10):6437–6446. [PubMed]
  • Lyons GE, Haselgrove J, Kelly AM, Rubinstein NA. Myosin transitions in developing fast and slow muscles of the rat hindlimb. Differentiation. 1983;25(2):168–175. [PubMed]
  • Lyons GE, Ontell M, Cox R, Sassoon D, Buckingham M. The expression of myosin genes in developing skeletal muscle in the mouse embryo. J Cell Biol. 1990 Oct;111(4):1465–1476. [PMC free article] [PubMed]
  • Mahdavi V, Periasamy M, Nadal-Ginard B. Molecular characterization of two myosin heavy chain genes expressed in the adult heart. Nature. 1982 Jun 24;297(5868):659–664. [PubMed]
  • Mahdavi V, Chambers AP, Nadal-Ginard B. Cardiac alpha- and beta-myosin heavy chain genes are organized in tandem. Proc Natl Acad Sci U S A. 1984 May;81(9):2626–2630. [PMC free article] [PubMed]
  • McNally EM, Buttrick PM, Leinwand LA. Ventricular myosin light chain 1 is developmentally regulated and does not change in hypertension. Nucleic Acids Res. 1989 Apr 11;17(7):2753–2767. [PMC free article] [PubMed]
  • Nadal-Ginard B, Mahdavi V. Molecular basis of cardiac performance. Plasticity of the myocardium generated through protein isoform switches. J Clin Invest. 1989 Dec;84(6):1693–1700. [PMC free article] [PubMed]
  • Nathan H, Gloobe H. Myocardial atrio-venous junctions and extensions (sleeves) over the pulmonary and caval veins. Anatomical observations in various mammals. Thorax. 1970 May;25(3):317–324. [PMC free article] [PubMed]
  • Pexieder T, Wenink AC, Anderson RH. A suggested nomenclature for the developing heart. Working Group for Embryology and Teratology of the European Society of Cardiology. Int J Cardiol. 1989 Dec;25(3):255–263. [PubMed]
  • Rovner AS, McNally EM, Leinwand LA. Complete cDNA sequence of rat atrial myosin light chain 1: patterns of expression during development and with hypertension. Nucleic Acids Res. 1990 Mar 25;18(6):1581–1586. [PMC free article] [PubMed]
  • Rudnicki MA, Jackowski G, Saggin L, McBurney MW. Actin and myosin expression during development of cardiac muscle from cultured embryonal carcinoma cells. Dev Biol. 1990 Apr;138(2):348–358. [PubMed]
  • Sassoon DA, Garner I, Buckingham M. Transcripts of alpha-cardiac and alpha-skeletal actins are early markers for myogenesis in the mouse embryo. Development. 1988 Sep;104(1):155–164. [PubMed]
  • Sassoon D, Lyons G, Wright WE, Lin V, Lassar A, Weintraub H, Buckingham M. Expression of two myogenic regulatory factors myogenin and MyoD1 during mouse embryogenesis. Nature. 1989 Sep 28;341(6240):303–307. [PubMed]
  • Schiaffino S, Samuel JL, Sassoon D, Lompré AM, Garner I, Marotte F, Buckingham M, Rappaport L, Schwartz K. Nonsynchronous accumulation of alpha-skeletal actin and beta-myosin heavy chain mRNAs during early stages of pressure-overload--induced cardiac hypertrophy demonstrated by in situ hybridization. Circ Res. 1989 May;64(5):937–948. [PubMed]
  • Schwartz K, Lecarpentier Y, Martin JL, Lompré AM, Mercadier JJ, Swynghedauw B. Myosin isoenzymic distribution correlates with speed of myocardial contraction. J Mol Cell Cardiol. 1981 Dec;13(12):1071–1075. [PubMed]
  • Schwartz K, Lompre AM, Bouveret P, Wisnewsky C, Whalen RG. Comparisons of rat cardiac myosins at fetal stages in young animals and in hypothyroid adults. J Biol Chem. 1982 Dec 10;257(23):14412–14418. [PubMed]
  • Sheer D, Morkin E. Myosin isoenzyme expression in rat ventricle: effects of thyroid hormone analogs, catecholamines, glucocorticoids and high carbohydrate diet. J Pharmacol Exp Ther. 1984 Jun;229(3):872–879. [PubMed]
  • Sissman NJ. Developmental landmarks in cardiac morphogenesis: comparative chronology. Am J Cardiol. 1970 Feb;25(2):141–148. [PubMed]
  • Soussi-Yanicostas N, Barbet JP, Laurent-Winter C, Barton P, Butler-Browne GS. Transition of myosin isozymes during development of human masseter muscle. Persistence of developmental isoforms during postnatal stage. Development. 1990 Feb;108(2):239–249. [PubMed]
  • Sweeney HL, Kushmerick MJ, Mabuchi K, Sréter FA, Gergely J. Myosin alkali light chain and heavy chain variations correlate with altered shortening velocity of isolated skeletal muscle fibers. J Biol Chem. 1988 Jun 25;263(18):9034–9039. [PubMed]
  • Sweeney LJ, Zak R, Manasek FJ. Transitions in cardiac isomyosin expression during differentiation of the embryonic chick heart. Circ Res. 1987 Aug;61(2):287–295. [PubMed]
  • Swynghedauw B. Developmental and functional adaptation of contractile proteins in cardiac and skeletal muscles. Physiol Rev. 1986 Jul;66(3):710–771. [PubMed]
  • Syrový I. Atrial and ventricular myosin ATPase--divergence with increasing animal species size. Pflugers Arch. 1985 May;404(1):80–82. [PubMed]
  • Virágh S, Challice CE. The development of the conduction system in the mouse embryo heart. Dev Biol. 1982 Jan;89(1):25–40. [PubMed]
  • Wagner PD, Stone DB. Myosin heavy chain-light chain recombinations and interactions between the two classes of light chains. J Biol Chem. 1983 Jul 25;258(14):8876–8882. [PubMed]
  • Wieczorek DF, Periasamy M, Butler-Browne GS, Whalen RG, Nadal-Ginard B. Co-expression of multiple myosin heavy chain genes, in addition to a tissue-specific one, in extraocular musculature. J Cell Biol. 1985 Aug;101(2):618–629. [PMC free article] [PubMed]
  • Weydert A, Daubas P, Lazaridis I, Barton P, Garner I, Leader DP, Bonhomme F, Catalan J, Simon D, Guénet JL, et al. Genes for skeletal muscle myosin heavy chains are clustered and are not located on the same mouse chromosome as a cardiac myosin heavy chain gene. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7183–7187. [PMC free article] [PubMed]
  • Whalen RG, Sell SM. Myosin from fetal hearts contains the skeletal muscle embryonic light chain. Nature. 1980 Aug 14;286(5774):731–733. [PubMed]
  • Whalen RG, Sell SM, Butler-Browne GS, Schwartz K, Bouveret P, Pinset-Härstöm I. Three myosin heavy-chain isozymes appear sequentially in rat muscle development. Nature. 1981 Aug 27;292(5826):805–809. [PubMed]
  • Wright WE, Sassoon DA, Lin VK. Myogenin, a factor regulating myogenesis, has a domain homologous to MyoD. Cell. 1989 Feb 24;56(4):607–617. [PubMed]
  • Zhang Y, Shafiq SA, Bader D. Detection of a ventricular-specific myosin heavy chain in adult and developing chicken heart. J Cell Biol. 1986 Apr;102(4):1480–1484. [PMC free article] [PubMed]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Gene
    Gene records that cite the current articles. Citations in Gene are added manually by NCBI or imported from outside public resources.
  • Gene (nucleotide)
    Gene (nucleotide)
    Records in Gene identified from shared sequence and PMC links.
  • GEO Profiles
    GEO Profiles
    Gene Expression Omnibus (GEO) Profiles of molecular abundance data. The current articles are references on the Gene record associated with the GEO profile.
  • HomoloGene
    HomoloGene clusters of homologous genes and sequences that cite the current articles. These are references on the Gene and sequence records in the HomoloGene entry.
  • MedGen
    Related information in MedGen
  • Nucleotide
    Primary database (GenBank) nucleotide records reported in the current articles as well as Reference Sequences (RefSeqs) that include the articles as references.
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem chemical substance records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records.

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...