Nkx2-5 suppresses the proliferation of atrial myocytes and conduction system

Circulation Research

Volumn 114, Issue 7, 2014, Pages 1103-1113

  Nakashima, Yasuhiro ^a   Yanez, Diana A ^a   Touma, Marlin ^b   Nakano, Haruko ^a   Jaroszewicz, Artur ^a   Jordan, Maria C ^b   Pellegrini, Matteo ^a   Roos, Kenneth P ^b   Nakano, Atsushi ^a,b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

atrial septal defect; atrioventricular block; congenital cardiac defect; internodal tract; mitosis; Nkx2 5; Notch

Indexed keywords

DOBUTAMINE; NOTCH RECEPTOR; TRANSCRIPTION FACTOR NKX2.5;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ATRIOVENTRICULAR BLOCK; ATRIOVENTRICULAR CONDUCTION; BRADYCARDIA; CELL CLONING; CELL PROLIFERATION; CONGESTIVE HEART FAILURE; CONTROLLED STUDY; ELECTROCARDIOGRAM; ELECTROCARDIOGRAPHY MONITORING; FLOW RATE; GENE DELETION; GENE EXPRESSION PROFILING; GENE INACTIVATION; GENE ONTOLOGY; HEART ATRIOVENTRICULAR NODE; HEART ATRIUM; HEART ATRIUM CONDUCTION; HEART ATRIUM MUSCLE; HEART ATRIUM SEPTUM; HEART ATRIUM SEPTUM DEFECT; HEART FORAMEN OVALE; HEART FUNCTION; HEART LEFT VENTRICLE EJECTION FRACTION; HEART MUSCLE CELL; HEART MUSCLE CONDUCTION SYSTEM; HEART VENTRICLE FUNCTION; HEMODYNAMICS; HOMOZYGOTE; IMMUNOHISTOCHEMISTRY; LUNG CIRCULATION; LUNG VASCULAR RESISTANCE; MITOSIS; MITOSIS RATE; MOUSE; NERVE BLOCK; NEWBORN; NONHUMAN; PRIORITY JOURNAL; PULMONARY HYPERTENSION; SIGNAL TRANSDUCTION; SINUS NODE;

ATRIAL SEPTAL DEFECT; ATRIOVENTRICULAR BLOCK; CONGENITAL CARDIAC DEFECT; INTERNODAL TRACT; MITOSIS; NKX2-5; NOTCH;

ANIMALS; CELL PROLIFERATION; HEART ATRIA; HEART CONDUCTION SYSTEM; HOMEODOMAIN PROTEINS; MICE; MICE, INBRED C57BL; MYOCYTES, CARDIAC; RECEPTORS, NOTCH; TRANSCRIPTION FACTORS; TRANSCRIPTOME;

EID: 84897474433     PISSN: 00097330     EISSN: 15244571     Source Type: Journal    
DOI: 10.1161/CIRCRESAHA.114.303219     Document Type: Article

References (59)

1. Fahed AC, Gelb BD, Seidman JG, Seidman CE. Genetics of congenital heart disease: the glass half empty. Circ Res. 2013;112:707-720.
2. Kathiresan S, Srivastava D. Genetics of human cardiovascular disease. Cell. 2012;148:1242-1257.
3. Soufan AT, van den Berg G, Ruijter JM, de Boer PA, van den Hoff MJ, Moorman AF. Regionalized sequence of myocardial cell growth and proliferation characterizes early chamber formation. Circ Res. 2006;99: 545-552.
4. Prall OW, Menon MK, Solloway MJ, et al. An Nkx2-5/Bmp2/Smad1 negative feedback loop controls heart progenitor specification and proliferation. Cell. 2007;128:947-959.
5. Sedmera D, Reckova M, DeAlmeida A, Coppen SR, Kubalak SW, Gourdie RG, Thompson RP. Spatiotemporal pattern of commitment to slowed proliferation in the embryonic mouse heart indicates progressive differentiation of the cardiac conduction system. Anat Rec A Discov Mol Cell Evol Biol. 2003;274:773-777.
6. Kruithof BP, van den Hoff MJ, Wessels A, Moorman AF. Cardiac muscle cell formation after development of the linear heart tube. Dev Dyn. 2003;227:1-13.
7. Anderson RH, Brown NA, Moorman AF. Development and structures of the venous pole of the heart. Dev Dyn. 2006;235:2-9.
8. Soufan AT, van den Hoff MJ, Ruijter JM, de Boer PA, Hagoort J, Webb S, Anderson RH, Moorman AF. Reconstruction of the patterns of gene expression in the developing mouse heart reveals an architectural arrangement that facilitates the understanding of atrial malformations and arrhythmias. Circ Res. 2004;95:1207-1215.
9. Melnyk P, Ehrlich JR, Pourrier M, Villeneuve L, Cha TJ, Nattel S. Comparison of ion channel distribution and expression in cardiomyocytes of canine pulmonary veins versus left atrium. Cardiovasc Res. 2005;65:104-116.
10. Komuro I, Izumo S. Csx: a murine homeobox-containing gene specifically expressed in the developing heart. Proc Natl Acad Sci USA. 1993;90:8145-8149.
11. Lints TJ, Parsons LM, Hartley L, Lyons I, Harvey RP. Nkx-2.5: a novel murine homeobox gene expressed in early heart progenitor cells and their myogenic descendants. Development. 1993;119:969.
12. Lyons I, Parsons LM, Hartley L, Li R, Andrews JE, Robb L, Harvey RP. Myogenic and morphogenetic defects in the heart tubes of murine embryos lacking the homeo box gene Nkx2-5. Genes Dev. 1995;9:1654-1666.
13. Tanaka M, Chen Z, Bartunkova S, Yamasaki N, Izumo S. The cardiac homeobox gene Csx/Nkx2.5 lies genetically upstream of multiple genes essential for heart development. Development. 1999;126:1269-1280.
14. Wu SM, Fujiwara Y, Cibulsky SM, Clapham DE, Lien CL, Schultheiss TM, Orkin SH. Developmental origin of a bipotential myocardial and smooth muscle cell precursor in the mammalian heart. Cell. 2006;127:1137-1150.
15. Nakano H, Liu X, Arshi A, Nakashima Y, van Handel B, Sasidharan R, Harmon AW, Shin JH, Schwartz RJ, Conway SJ, Harvey RP, Pashmforoush M, Mikkola HK, Nakano A. Haemogenic endocardium contributes to transient definitive haematopoiesis. Nat Commun. 2013;4:1564.
16. Schott JJ, Benson DW, Basson CT, Pease W, Silberbach GM, Moak JP, Maron BJ, Seidman CE, Seidman JG. Congenital heart disease caused by mutations in the transcription factor NKX2-5. Science. 1998;281:108-111.
17. Goldmuntz E, Geiger E, Benson DW. NKX2.5 mutations in patients with tetralogy of fallot. Circulation. 2001;104:2565-2568.
18. McElhinney DB, Geiger E, Blinder J, Benson DW, Goldmuntz E. NKX2.5 mutations in patients with congenital heart disease. J Am Coll Cardiol. 2003;42:1650-1655.
19. Gutierrez-Roelens I, De Roy L, Ovaert C, Sluysmans T, Devriendt K, Brunner HG, Vikkula M. A novel CSX/NKX2-5 mutation causes autosomal-dominant AV block: are atrial fibrillation and syncopes part of the phenotype? Eur J Hum Genet. 2006;14:1313-1316.
20. Kasahara H, Wakimoto H, Liu M, Maguire CT, Converso KL, Shioi T, Huang WY, Manning WJ, Paul D, Lawitts J, Berul CI, Izumo S. Progressive atrioventricular conduction defects and heart failure in mice expressing a mutant Csx/Nkx2.5 homeoprotein. J Clin Invest. 2001;108:189-201.
21. Jay PY, Harris BS, Maguire CT, Buerger A, Wakimoto H, Tanaka M, Kupershmidt S, Roden DM, Schultheiss TM, O'Brien TX, Gourdie RG, Berul CI, Izumo S. Nkx2-5 mutation causes anatomic hypoplasia of the cardiac conduction system. J Clin Invest. 2004;113:1130-1137.
22. Pashmforoush M, Lu JT, Chen H, et al. Nkx2-5 pathways and congenital heart disease; loss of ventricular myocyte lineage specification leads to progressive cardiomyopathy and complete heart block. Cell. 2004;117:373-386
23. Briggs LE, Takeda M, Cuadra AE, et al. Perinatal loss of Nkx2-5 results in rapid conduction and contraction defects. Circ Res. 2008;103:580-590.
24. Terada R, Warren S, Lu JT, Chien KR, Wessels A, Kasahara H. Ablation of Nkx2-5 at mid-embryonic stage results in premature lethality and cardiac malformation. Cardiovasc Res. 2011;91:289-299.
25. deAlmeida A, McQuinn T, Sedmera D. Increased ventricular preload is compensated by myocyte proliferation in normal and hypoplastic fetal chick left ventricle. Circ Res. 2007;100:1363-1370.
26. Ho SY, Anderson RH, Sánchez-Quintana D. Atrial structure and fibres: morphologic bases of atrial conduction. Cardiovasc Res. 2002;54: 325-336.
27. Anderson RH, Cook AC. The structure and components of the atrial chambers. Europace. 2007;9(suppl 6):vi3-vi9.
28. Kruithof BP, Van Den Hoff MJ, Tesink-Taekema S, Moorman AF. Recruitment of intra-and extracardiac cells into the myocardial lineage during mouse development. Anat Rec A Discov Mol Cell Evol Biol. 2003;271:303-314.
29. Moorman AF, Christoffels VM. Cardiac chamber formation: development, genes, and evolution. Physiol Rev. 2003;83:1223-1267.
30. Snarr BS, O'Neal JL, Chintalapudi MR, Wirrig EE, Phelps AL, Kubalak SW, Wessels A. Isl1 expression at the venous pole identifies a novel role for the second heart field in cardiac development. Circ Res. 2007;101:971-974.
31. Nakano H, Williams E, Hoshijima M, Sasaki M, Minamisawa S, Chien KR, Nakano A. Cardiac origin of smooth muscle cells in the inflow tract. J Mol Cell Cardiol. 2011;50:337-345.
32. Xu XF, Lv Y, Gu WZ, Tang LL, Wei JK, Zhang LY, Du LZ. Epigenetics of hypoxic pulmonary arterial hypertension following intrauterine growth retardation rat: epigenetics in PAH following IUGR. Respir Res. 2013;14:20.
33. Danhaive O, Margossian R, Geva T, Kourembanas S. Pulmonary hypertension and right ventricular dysfunction in growth-restricted, extremely low birth weight neonates. J Perinatol. 2005;25:495-499.
34. Rosenberg A. The IUGR newborn. Semin Perinatol. 2008;32:219-224.
35. Biben C, Weber R, Kesteven S, Stanley E, McDonald L, Elliott DA, Barnett L, Köentgen F, Robb L, Feneley M, Harvey RP. Cardiac septal and valvular dysmorphogenesis in mice heterozygous for mutations in the homeobox gene Nkx2-5. Circ Res. 2000;87:888-895.
36. Mommersteeg MT, Brown NA, Prall OW, de Gier-de Vries C, Harvey RP, Moorman AF, Christoffels VM. Pitx2c and Nkx2-5 are required for the formation and identity of the pulmonary myocardium. Circ Res. 2007;101:902-909.
37. Rinkevich Y, Lindau P, Ueno H, Longaker MT, Weissman IL. Germ-layer and lineage-restricted stem/progenitors regenerate the mouse digit tip. Nature. 2011;476:409-413.
38. Christoffels VM, Mommersteeg MT, Trowe MO, Prall OW, de Gier-de Vries C, Soufan AT, Bussen M, Schuster-Gossler K, Harvey RP, Moorman AF, Kispert A. Formation of the venous pole of the heart from an Nkx2-5-negative precursor population requires Tbx18. Circ Res. 2006;98:1555-1563.
39. Mommersteeg MT, Hoogaars WM, Prall OW, de Gier-de Vries C, Wiese C, Clout DE, Papaioannou VE, Brown NA, Harvey RP, Moorman AF, Christoffels VM. Molecular pathway for the localized formation of the sinoatrial node. Circ Res. 2007;100:354-362.
40. Sakata Y, Koibuchi N, Xiang F, Youngblood JM, Kamei CN, Chin MT. The spectrum of cardiovascular anomalies in CHF1/Hey2 deficient mice reveals roles in endocardial cushion, myocardial and vascular maturation. J Mol Cell Cardiol. 2006;40:267-273.
41. Cho HS, Hayami S, Toyokawa G, Maejima K, Yamane Y, Suzuki T, Dohmae N, Kogure M, Kang D, Neal DE, Ponder BA, Yamaue H, Nakamura Y, Hamamoto R. RB1 methylation by SMYD2 enhances cell cycle progression through an increase of RB1 phosphorylation. Neoplasia. 2012;14:476-486.
42. Bovolenta P, Esteve P, Ruiz JM, Cisneros E, Lopez-Rios J. Beyond Wnt inhibition: new functions of secreted Frizzled-related proteins in development and disease. J Cell Sci. 2008;121:737-746.
43. Grego-Bessa J, Luna-Zurita L, del Monte G, et al. Notch signaling is essential for ventricular chamber development. Dev Cell. 2007;12:415-429.
44. Campa VM, Gutiérrez-Lanza R, Cerignoli F, Díaz-Trelles R, Nelson B, Tsuji T, Barcova M, Jiang W, Mercola M. Notch activates cell cycle reentry and progression in quiescent cardiomyocytes. J Cell Biol. 2008;183:129-141.
45. Collesi C, Zentilin L, Sinagra G, Giacca M. Notch1 signaling stimulates proliferation of immature cardiomyocytes. J Cell Biol. 2008;183:117-128.
46. Rentschler S, Yen AH, Lu J, Petrenko NB, Lu MM, Manderfield LJ, Patel VV, Fishman GI, Epstein JA. Myocardial Notch signaling reprograms cardiomyocytes to a conduction-like phenotype. Circulation. 2012;126:1058-1066.
47. Murtaugh LC, Stanger BZ, Kwan KM, Melton DA. Notch signaling controls multiple steps of pancreatic differentiation. Proc Natl Acad Sci USA. 2003;100:14920-14925.
48. Tanaka M, Berul CI, Ishii M, et al. A mouse model of congenital heart disease: cardiac arrhythmias and atrial septal defect caused by haploinsufficiency of the cardiac transcription factor csx/nkx2.5. Cold Spring Harb Symp Quant Biol. 2002;67:317-325
49. Takeda M, Briggs LE, Wakimoto H, Marks MH, Warren SA, Lu JT, Weinberg EO, Robertson KD, Chien KR, Kasahara H. Slow progressive conduction and contraction defects in loss of Nkx2-5 mice after cardiomyocyte terminal differentiation. Lab Invest. 2009;89:983-993.
50. Targoff KL, Schell T, Yelon D. Nkx genes regulate heart tube extension and exert differential effects on ventricular and atrial cell number. Dev Biol. 2008;322:314-321.
51. Holsinger JW Jr, Wallace AG, Sealy WC. The identification and surgical significance of the atrial internodal conduction tracts. Ann Surg. 1968;167:447-453.
52. James TN, Sherf L. Specialized tissues and preferential conduction in the atria of the heart. Am J Cardiol. 1971;28:414-427.
53. Hoogaars WM, Tessari A, Moorman AF, de Boer PA, Hagoort J, Soufan AT, Campione M, Christoffels VM. The transcriptional repressor Tbx3 delineates the developing central conduction system of the heart. Cardiovasc Res. 2004;62:489-499.
54. Ito H, Iwasaki K, Ikeda T, Sakai H, Shimokawa I, Matsuo T. HNK-1 expression pattern in normal and bis-diamine induced malformed developing rat heart: three dimensional reconstruction analysis using computer graphics. Anat Embryol (Berl). 1992;186:327-334.
55. Bressan M, Liu G, Mikawa T. Early mesodermal cues assign avian cardiac pacemaker fate potential in a tertiary heart field. Science. 2013;340:744-748.
56. Meysen S, Marger L, Hewett KW, Jarry-Guichard T, Agarkova I, Chauvin JP, Perriard JC, Izumo S, Gourdie RG, Mangoni ME, Nargeot J, Gros D, Miquerol L. Nkx2.5 cell-autonomous gene function is required for the postnatal formation of the peripheral ventricular conduction system. Dev Biol. 2007;303:740-753.
57. Pierpont ME, Basson CT, Benson DW Jr, Gelb BD, Giglia TM, Goldmuntz E, McGee G, Sable CA, Srivastava D, Webb CL. Genetic basis for congenital heart defects: current knowledge: a scientific statement from the american heart association congenital cardiac defects committee, council on cardiovascular disease in the young: endorsed by the American Academy of Pediatrics. Circulation. 2007;115:3015-3038.
58. Hatcher CJ, Kim MS, Mah CS, Goldstein MM, Wong B, Mikawa T, Basson CT. TBX5 transcription factor regulates cell proliferation during cardiogenesis. Dev Biol. 2001;230:177-188.
59. Gelb BD, Tartaglia M. Noonan syndrome and related disorders: dysregulated RAS-mitogen activated protein kinase signal transduction. Hum Mol Genet. 2006;15:R220-R226.