Abstract
In this study we present data on the spatial relationship between neural crest-derived cells (NCC) and the specialized cardiac conduction system (CCS) in the developing murine heart. Using Wnt1-Cre/R26R conditional reporter mice that express β-galactosidase from ROSA26 upon Cre-mediated recombination, two populations of NCC are seen: one migrates through the arterial pole and contributes to the bundle branches, whereas the second population enters by way of the venous pole and provides cells to the sinoatrial and atrioventricular node areas. The CCS/lacZ construct is found in the myocardium of the early embryonic heart and afterward only persists in the definitive CCS and is acknowledged as a reporter for the developing conduction system. The contiguous expression of both reporters is suggestive for a potential role of cardiac NCC in the induction of the final differentiation of the CCS.
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References
Azhar M, Schultz JJ, Grupp I, Dorn GW II, Meneton P, Molin DGM, Gittenberger-de Groot AC, Doetschman T (2003) Transforming growth factor beta in cardiovascular development and function. Cytokine Growth Factor Rev 14:391–407
Bartram U, Molin DGM, Wisse LJ, Azhar M, Sanford LP, Doetschman T, Speer CP, Poelmann RE, Gittenberger-de Groot AC (2001) Double-outlet right ventricle and overriding tricuspid valve reflect disturbances of looping, myocardialization, endocardial cushion differentiation, and apoptosis in TGFβ2-knockout mice. Circulation 2745–2752
Bergwerff M, Verberne ME, DeRuiter MC, Poelmann RE, Gittenberger-de Groot AC (1998) Neural crest cell contribution to the developing circulatory system. Implications for vascular morphology? Circ Res 82:221–231
Blom NA, Gittenberger-de Groot AC, DeRuiter MC, Poelmann RE, Mentink MMT, Ottenkamp J (1999) Development of the cardiac conduction tissue in human embryos using HNK-1 antigen expression: possible relevance for understanding of abnormal atrial automaticity. Circulation 99:800–806
Cheng G, Litchenberg WH, Cole GJ, Mikawa T, Thompson RP, Gourdie RG (1999) Development of the cardiac conduction system involves recruitment within a multipotent cardiomyogenic lineage. Development 126:5041–5049
Epstein JA, Li J, Lang D, Chen F, Brown CB, Jin F, Lu MM, Thomas M, Liu E, Wessels A, Lo CW (2000) Migration of cardiac neural crest cells in Splotch embryos. Development 127:1869–1878
Gorza L, Schiaffino S, Vitadello M (1988) Heart conduction system: a neural crest derivative? Brain Res 457:360–366
Gourdie RG, Mima T, Thompson RP, Mikawa T (1995) Terminal diversification of the myocyte lineage generates Purkinje fibers of the cardiac conduction system. Development 121:1423–1431
Jiang X, Rowitch DH, Soriano P, McMahon AP, Sucov HM (2000) Fate of the mammalian cardiac neural crest. Development 127:1607–1616
Jongbloed MR, Schalij MJ, Poelmann RE, Blom NA, Fekkes ML, Wang Z, Fishman GI, Gittenberger-de Groot AC (2004) Embryonic conduction tissue: a spatial correlation with adult arrhythmogenic areas. J Cardiovasc Electrophysiol 15:349–355
Kirby ML, Gale TF, Stewart DE (1983) Neural crest cells contribute to normal aorticopulmonary septation. Science 220:1059–1061
LeDouarin NM (1980) Migration and differentiation of neural crest cells. Curr Top Dev Biol 16:31–85
Molin DGM, Bartram U, VanderHeiden K, VanIperen L, Speer CP, Hierck BP, Poelmann RE, Gittenberger-de Groot AC (2003) Expression patterns of TGFβ1–3 associate with myocardialisation of the outflow tract and the development of the epicardium and the fibrous heart skeleton. Dev Dyn 227:431–444
Poelmann RE, Gittenberger-de Groot AC (1999) A subpopulation of apoptosis-prone cardiac neural crest cells targets to the venous pole: multiple functions in heart development? Dev Biol 207:271–286
Poelmann RE, Mikawa T, Gittenberger-de Groot AC (1998) Neural crest cells in outflow tract septation of the embryonic chicken heart: differentiation and apoptosis. Dev Dyn 212:373–384
Rentschler S, Vaidya DM, Tamaddon H, Degenhardt K, Sassoon D, Morley GE, Jalife J, Fishman GI (2001) Visualization and functional characterization of the developing murine cardiac conduction system. Development 128:1785–1792
Rentschler S, Zander J, Meyers K, France D, Levine R, Porter G, Rivkees SA, Morley GE, Fishman GI (2002) Neuregulin-1 promotes formation of the murine cardiac conduction system. Proc Natl Acad Sci U S A 99:10464–10469
Sanford LP, Ormsby I, Gittenberger-de Groot AC, Sariola H, Friedman R, Boivin GP, Cardell EL, Doetschman T (1997) TGFβ2 knockout mice have multiple developmental defects that are non-overlapping with other TGFβ knockout phenotypes. Development 124:2659–2670
Verberne ME, Gittenberger-de Groot AC, Poelmann RE (1999) Contribution of the cervical sympathetic ganglia to the innervation of the pharyngeal arch arteries and the heart in the chick embryo. Anat Rec 255:407–419
Waldo KL, Lo CW, Kirby ML (1999) Connexin 43 expression reflects neural crest patterns during cardiovascular development. Dev Biol 208:307–323
Acknowledgements
This work was supported by HL64757 (G.I.F.) and HD26471 (T.D.) from the National Institutes of Health and a Burroughs Wellcome Fund Clinical Scientist Award in Translational Research (G.I.F.). Henry M. Sucov is acknowledged for the Wnt1-Cre/R26R sections that have been described previously (Jiang et al. 2000). Bruce Aronow and Sue Kong are acknowledged for analyzing microarray data.
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Poelmann, R.E., Jongbloed, M.R.M., Molin, D.G.M. et al. The neural crest is contiguous with the cardiac conduction system in the mouse embryo: a role in induction?. Anat Embryol 208, 389–393 (2004). https://doi.org/10.1007/s00429-004-0401-6
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DOI: https://doi.org/10.1007/s00429-004-0401-6