Biopolym. Cell. 2013; 29(2):124-130.
http://dx.doi.org/10.7124/bc.00080F
Structure and Function of Biopolymers
Embryonically induced β-catenin haploinsufficiency attenuates postnatal heart development and causes violation of foetal genes program
1, 2Palchevska O. L., 1, 2Balatskii V. V., 1, 2Andrejeva A. O., 1Macewicz L. L., 1Piven O. O., 1Lukash L. L.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680
  2. Educational and Scientific Center "Institute of Biology",
    Taras Shevchenko National University of Kyiv
    64/13, Volodymyrska Str., Kyiv, Ukraine, 01601

Abstract

The β-catenin role in myocardium remodeling and hypertrophy development is the subject of numerous and controversial investigations. Aim. To investigate the significance of cardiac ablation of β-catenin for heart development using conditional knockout approach. Methods. Standard histological techniques (HE- and MT-staining) and quantitative RT-PCR were used. Results. Our data demonstrate that β-catenin haploinsufficiency in heart provokes upregulation of foetal genes program without visible morphological abnormalities comparing to control groups of animals of the same age. Conclusions. Our data demonstrate that experimental conditions in this study provoke the delay in the development and growth of adult heart without visible morphological abnormalities.
Keywords: heart development, β-catenin, Wnt-signaling, heart remodeling, hypertrophic response
Full text: (PDF, in English)

References

[1] Nadal-Ginard B., Kajstura J., Leri A., Anversa P. Myocyte death, growth, and regeneration in cardiac hypertrophy and failure Circ. Res 2003 92, N 2:139–150.
[2] Brade T., Manner J., Kuhl M. The role of Wnt signalling in cardiac development and tissue remodeling in the mature heart Cardiovasc. Res 2006 72, N 2:198–209.
[3] Malekar P., Hagenmueller M., Anyanwu A., Buss S., Streit M. R., Weiss C. S., Wolf D., Riffel J., Bauer A., Katus H. A., Hardt S. E. Wnt signaling is critical for maladaptive cardiac hypertrophy and accelerates myocardial remodeling Hypertension 2010 55, N 4:939–945.
[4] Grigoryan T., Wend P., Klaus A., Birchmeier W. Deciphering the function of canonical Wnt signals in development and disease: Conditional lossand gain-of-function mutations of beta-catenin in mice Genes Dev 2008 22, N17 P. 2308–2341.
[5] Lickert H., Kutsch S., Kanzler B., Tamai Y., Taketo M. M., Kemler R. Formation of multiple hearts in mice following deletion of beta-catenin in the embryonic endoderm Dev. Cell 2002 3, N 2 P. 171–181.
[6] Cadigan K. M., Peifer M. Wnt signaling from development to disease: insights from model systems Cold Spring Harb. Perspect. Biol 2009 1, N 2 a002881.
[7] Bergmann M. W. WNT signaling in adult hypertrophy and remodeling: lessons learned from cardiac development Circ. Res 2010 107, N 10 P. 1198–1208.
[8] Gordon M. D., Nusse R. Wnt signaling: multiple pathways, multiple receptors, and multiple transcription factors J. Biol. Chem 2006 281, N 32 P. 22429–22433.
[9] Rao T. P., Kuhl M. An updated overview on Wnt signaling pathways: a prelude for more Circ. Res 2010 106, N 12 P. 1798–1806.
[10] Archbold H. C., Yang Y. X., Chen L., Cadigan K. M. How do they do Wnt they do?: regulation of transcription by the Wnt/b-catenin pathway Acta. Physiol. (Oxf) 2012 204, N 1:74–109.
[11] Nusse R. Wnt signaling and stem cell control Cell Res 2008 18, N 5:523–527.
[12] Klaus A., Muller M., Schulz H., Saga Y., Martin J. F., Birchmeier W. Wnt/b-catenin and Bmp signals control distinct sets of transcription factors in cardiac progenitor cells Proc. Natl Acad. Sci. USA 2012 109, N 27 P. 10921–10926.
[13] Gessert S., Kuhl M. The multiple phases and faces of Wnt signaling during cardiac differentiation and development Circ. Res 2010 107, N 2 P. 186–199.
[14] Haegel H., Larue L., Ohsugi M., Fedorov L., Herrenknecht K., Kemler R. Lack of beta-catenin affects mouse development at gastrulation Development 1995 121, N 11 P. 3529–3537.
[15] Huelsken J., Vogel R., Brinkmann V., Erdmann B., Birchmeier C., Birchmeier W. Requirement for beta-catenin in anteriorposterior axis formation in mice J. Cell. Biol 2000 148, N 3 P. 567–578.
[16] Lickert H., Kutsch S., Kanzler B., Tamai Y., Taketo M. M., Kemler R. Formation of multiple hearts in mice following deletion of beta-catenin in the embryonic endoderm Dev. Cell 2002 3, N 2 P. 171–181.
[17] Piven O. O., Kostetskii I. E., Macewicz L. L., Kolomijec Y. M., Radice G. L., Lukash L. L. Requirement for N-cadherin-catenin complex in heart development Exp. Biol. Med. (Maywood) 2011 236, N 7 P. 816–822.
[18] Qu J., Zhou J., Yi X. P., Dong B., Zheng H., Miller L. M., Wang X., Schneider M. D., Li F. Cardiac-specific haploinsufficiency of beta-catenin attenuates cardiac hypertrophy but enhances fetal gene expression in response to aortic constriction J. Mol. Cell. Cardiol 2007 43, N 3. P. 319–326.
[19] Butz S., Stappert J., Weissig H., Kemler R. Plakoglobin and beta-catenin: distinct but closely related Science 1992 257, N 5073 P. 1142–1144.
[20] Zhou J., Qu J., Yi X. P., Graber K., Huber L., Wang X., Gerdes A. M., Li F. Upregulation of gamma-catenin compensates for the loss of beta-catenin in adult cardiomyocytes Am. J. Physiol. Heart Circ. Physiol 2007 292, N 1 H270–H276.
[21] Swope D., Cheng L., Gao E., Li J., Radice G. L. Loss of cadherin-binding proteins, b-catenin and plakoglobin, in the heart leads to gap junction remodelling and arrhythmogenesis Mol. Cell. Biol 2012 32, N 6 P. 1056–1067.
[22] Haq S., Michael A., Andreucci M., Bhattacharya K., Dotto P., Walters B., Woodgett J., Kilter H., Force T. Stabilization of beta-catenin by a Wnt-independent mechanism regulates cardiomyocyte growth Proc. Natl Acad. Sci. USA 2003 100, N 8 P. 4610–4615.
[23] Liu X., Rubin J. S., Kimmel A. R. Rapid, Wnt-induced changes in GSK3beta associations that regulate beta-catenin stabilization are mediated by Galpha proteins Curr. Biol 2005 15, N 22 P. 1989–1997.
[24] Chen X., Shevtsov S. P., Hsich E., Cui L., Haq S., Aronovitz M., Kerkela R., Molkentin J. D., Liao R., Salomon R. N., Petten R., Force T. The beta-catenin/T-cell factor/lymphocyte enhancer factor signaling pathway is required for normal and stress induced cardiac hypertrophy Mol. Cell. Biol 2006 26, N 12 P. 4462–4473.
[25] Hirschy A., Croquelois A., Perriard E., Schoenauer R., Agarkova I., Hoerstrup S. P., Taketo M. M., Pedrazzini T., Perriard J. C., Ehler E. Stabilised beta-catenin in postnatal ventricular myocardium leads to dilated cardiomyopathy and premature death Basic Res. Cardiol 2010 105, N 5 P. 597–608.
[26] Hahn J. Y., Cho H. J., Bae J. W., Yuk H. S., Kim K. I., Park K. W., Koo B. K., Chae I. H., Shin C. S., Oh B. H., Choi Y. S., Park Y. B., Kim H. S. Beta-catenin overexpression reduces myocardial infarct size through differential effects on cardiomyocytes and cardiac fibroblasts J. Biol. Chem 2006 281, N 41 P. 30979– 30989.
[27] Baurand A., Zelarayan L., Betney R., Gehrke C., Dunger S., Noack C., Busjahn A., Huelsken J., Taketo M. M., Birchmeier W., Dietz R., Bergmann M. W. Beta-catenin downregulation is required for adaptive cardiac remodeling Circ. Res 2007 100, N 9 P. 1353–1362.
[28] Lyons G. E., Schiaffino S., Sassoon D., Barton P., Buckingham M. Developmental regulation of myosin gene expression in mouse cardiac muscle J. Cell. Biol 1990 111, N 6, Pt 1 P. 2427–2436.
[29] Agah R., Frenkel P. A., French B. A., Michael L. H., Overbeek P. A., Schneider M. D. Gene recombination in postmitotic cells. Targeted expression of Cre recombinase provokes cardiacrestricted, site-specific rearrangement in adult ventricular muscle in vivo J. Clin. Invest 1997 100, N 1 P. 169–179.
[30] Nagy A., Gertsenstein M., Vintersten K., Behringer R. Manipulating the mouse embryo: A laboratory manual New York: Cold Spring Harbor Lab. Press, 2003 234 p.
[31] Palermo J., Gulick J., Colbert M., Fewell J., Robbins J. Transgenic remodeling of the contractile apparatus in the mammalian heart Circ. Res 1996 78, N 3: 504–509.
[32] Izumo S., Lompre A. M., Matsuoka R., Koren G., Schwartz K., Nadal-Ginard B., Mahdavi V. Myosin heavy chain messenger RNA and protein isoform transitions during cardiachypertrophy. Interaction between hemodynamic and thyroid hormoneinduced signals J. Clin. Invest 1987 79, N 3:970–977.
[33] Besse S., Assayag P., Delcayre C., Carre F., Cheav S. L., Lecarpentier Y., Swynghedauw B. Normal and hypertrophied senescent rat heart:mechanical and molecular characteristics Am. J. Physiol 1993 265, N 1 Pt 2 H183–H190.
[34] Lowes B. D., Minobe W., Abraham W. T., Rizeq M. N., Bohlmeyer T. J., Quaife R. A., Roden R. L., Dutcher D. L., Robertson A. D., Voelkel N. F., Badesch D. B., Groves B. M., Gilbert E. M., Bristow M. R. Changes in gene expression in the intact human heart. Downregulation of alpha-myosin heavy chain in hypertrophied, failing ventricular myocardium J. Clin. Invest 1997 100, N 9:2315–2324.
[35] Li J., Swope D., Raess N., Cheng L., Muller E. J., Radice G. L. Cardiac tissue-restricted deletion of plakoglobin results in progressive cardiomyopathy and activation of {beta}-catenin signaling Mol. Cell. Biol 2011 31, N 6:1134–1144.
[36] Vanderheyden M., Bartunek J., Goethals M. Brain and other natriuretic peptides: molecular aspects Eur. J. Heart Fail 2004 6, N 3 P. 261–268.
[37] Tamura N., Ogawa Y., Chusho H., Nakamura K., Nakao K., Suda M., Kasahara M., Hashimoto R., Katsuura G., Mukoyama M., Itoh H., Saito Y., Tanaka I., Otani H., Katsuki M. Cardiac fibrosis in mice lacking brain natriuretic peptide Proc. Natl Acad. Sci. USA 2000 97, N 8 P. 4239–4244.