Abstract
To investigate the origin and development of the cardiac conduction system, the distribution of HNK-1 immunoreactivity in embryonic rat hearts was studied in histological sections and in three-dimensional computer reconstructions. Earliest HNK-1 reactivity was found along the endocardial surface of the fusing tubular heart at 9.5 embryonic days (ED) and subsequently within individual myocytes scattered widely along the looped tubular heart. Immunopositive myocytes appeared along the earliest ventricular trabeculae as they coalesced to form the developing interventricular septum during day 11, spreading to either side to give rise to the right and left bundle branches in the 12.5 ED heart. In the venous pole of the heart, primordia of the sinus node, and of the transient left sinus node, appeared immunopositive from 12.5 ED, coalescing during ED 13 along the anterior wall of the right sinus horn or developing coronary sinus, respectively. In the atria, several distinct tracts of immunoreactive myocytes were defined by 14.5 ED, ramifying from the sinoatrial junction to the atrial appendages or to the atrio-ventricular (AV) junction near the AV node. The timing and distribution of these immunostaining patterns suggest that ventricular conduction tissue develops within the earliest trabecular and septal myocardium, and is distinct from later immunopositive atrial tracts and extracardiac cell populations, such as neural crest, that appear to contribute to formation of the sinus node and autonomic innervation of the heart.
Similar content being viewed by others
References
Abo T, Balch CM (1981) A differentiation antigen of human NK and K cells identified by a monoclonal antibody (HNK-1). J Immunol 127:1024–1029
Anderson RH, Becker AE, Brechenmacher C, Davies MJ, Rossi L (1975) The human atrioventricular junctional area. A morphological study of the A-V node and bundle. Eur J Cardiol 3:11–25
Anderson RH, Becker AE, Wenink ACG, Janse MJ (1976) The development of the cardiac specialized tissue. In: Wellens HJJ, Lie KI, Janse MJ (eds) The conduction system of the heart. Nijhoff, Hague, pp 3–28
Benninghoff A (1924) Über die beziehungen des Reizleitungssystems und der Papillarmuskeln zu den Konturfasern des Herzschlauches. Verh Anat Ges 32:185–208
Brown NA, Fabro S (1981) Quantitation of rat embryonic development in vitro: a morphological scoring system. Teratology 24:65–78
Domenech-Mateu JM, Arno-Palan A, Martinez-Pozo A (1991) Study of the development of the atrioventricular conduction system as a consequence of observing an extra atrioventricular node in the normal heart of a human fetus. Anat Rec 230:73–85
Fukiishi Y, Morriss-Kay GH (1992) Migration of cranial neural crest cells to the pharyngeal arches and heart in rat embryos. Cell Tissue Res 268:1–8
Gardener E, O'Rahilly R (1976) The nerve supply and conducting system of the human heart at the end of the embryonic period proper. J Anat 121:571–587
Gorza L, Schiaffino S, Vitadello M (1988) Heart conduction system: a neural crest derivative? Brain Res 457:360–366
Gourdie RG, Green CR, Thompson RP, Severs NJ (1990) Three-dimensional reconstruction of gap junction arrangement in developing and adult rat heart. Trans R Microsc Soc 1(90): 417–420
Gourdie RG, Green CR, Severs NJ, Thompson RP (1992) Immunolabelling patterns of gap junction connexins in the developing and mature rat heart. Anat Embryol 185:363–378
de Groot IJM, Lamers WH. Moorman AFM (1989) Isomyosin expression patterns during rat heart morphogenesis: an immunohistochemical study. Anat Rec 224:365–373
Heintzberger CFM (1974) The development of the sinu-atrial node in the mouse. Acta Morphol Neerl-Scand 12:317–330
Ikeda T, Iwasaki K, Shimokawa I, Sakai H, Ito H, Matsuo T (1990) Leu-7 immunoreactivity in human and rat embryonic hearts, with special reference to the development of the conduction tissue. Anat Embryol 182:553–562
James TN, Sherf L (1971) Specialized tissues and preferential conduction in the atria of the heart. Am J Cardiol 28:414–427
Janse MJ, Anderson RH (1974) Specialized internodal atrial pathways — fact or fiction? Eur J Cardiol 2/2:117–136
van Kempen MJA, Gros D, Moorman AFM, Lamers WH (1991) Distribution of connexin 43 in the adult and developing rat heart. Circ Res 68:1638–1651
Kirby ML, Gale TF, Stewart DE (1983) Neural crest cells contribute to aorticopulmonary septation. Science 220:1059–1061
Kuratani SC, Kirby ML (1991) Initial migration and distribution of the cardiac neural crest in the avian embryo. Am J Anat 191:215–227
Kuruk N, Franke WW (1988) Transient co-expression of desmin and cytokeratins 8 and 18 in developing myocardial cells of some vertebrate species. Differentiation 38:177–193
Lamers WH, te Kortschot A, Los JA, Moorman AFM (1987) Acetylcholinesterase in prenatal rat heart: a marker for the early development of the cardiac conductive tissue? Anat Rec 217:361–370
Lamers WH, Wessels A, Verbeek FJ, Moorman AFM, Viragh S, Wenink ACG, Gittenberger-de Groot AC, Anderson AH (1992) New findings concerning ventricular septation in the human heart. Circulation 86:1194–1205
Le Lievre CS, Le Douarin NM (1975) Mesenchymal derivatives of the neural crest: analysis of chimaeric quail and chick embryos. J Embryol Exp Morphol 34:125–154
Mall FP (1912) On the development of the human heart. Am J Anat 13:249–298
Manasek FJ (1968) Embryonic development of the heart. I. A light and electron microscopic study of myocardial development in the chick embryo. J Morphol 125:329–366
Manasek FJ (1969) Embryonic development of the heart. II. Formation of the epicardium. J Embryol Exp Morphol 22:333–348
Marino TA, Truex RC, Marino DR (1979) The development of the atrioventricular node and bundle in the ferret heart. Am J Anat 154:135–150
McCabe CF, Thompson RP, Cole GC (1990) Distribution of a novel developmentally regulated polypeptide expressed in cardiac and neural tissues during embryogenesis. J Cell Biol 111:243a
Meijler FL, Janse MJ (1988) Morphology and electrophysiology of the mammalian atrioventricular node. Physiol Rev 62:608–647
Metcalfe WK, Myers PZ, Trevarrow B, Bass MB, Kimmel CB (1990) Primary neurons that express the L2/HNK-1 carbohydrate during early development in the zebra fish. Development 110:491–504
Miyagawa ST, Takao A, Tomita H, Kirby ML (1989) Cardiac neural crest cells may contribute to the conduction system in the chick heart. Circulation 80:165a
Newgreen DF, Powel ME, Moser B (1990) Spatiotemporal changes in HNK-1/L2 glyconjugates on avian embryo somite and neural crest cells. Dev Biol 139:100–120
Nishibatake M, Kirby ML, Van Mierop LHS (1987) Pathogenesis of persistent truncus arteriosus and dextroposed aorta in the chick embryo after neural crest ablation. Circulation 75:255–264
Patten BM (1956) The development of the sino-ventricular conduction system. Univ Mich Med Bull 22:1–21
Racker DK (1989) Atrioventricular node and input pathways: a correlated gross anatomical and histological study of the canine atrioventricular junctional region. Anat Rec 224:336–354
Rubenstein DS, Fox LM, McNulty JA, Lipsius SL (1987) Electrophysiology and ultrastructure of Eustachian ridge from cat right atrium: a comparison with SA node. J Mol Cell Cardiol 19:965–976
Sanders E, de Groot IJM, Geerts WJC, de Jong F, van Horssen AA, Los JA, Moorman AFM (1986) The local expression of adult chicken heart myosins during development II. Ventricular conducting tissue. Anat Embryol 174:187–193
Sumida H, Akimoto N, Nakamura H (1989) Distribution of the neural crest cells in the heart of birds: a three dimensional analysis. Anat Embryol 180:29–35
Tan SS, Morriss-Kay GM (1986) Analysis of cranial neural crest cell migration and early fates in postimplantation rat chimaeras. J Embryol Exp Morphol 98:21–58
Thompson RP, Simson JAV, Currie MG (1986) Atriopeptin distribution in the developing rat heart. Anat Embryol 175:227–233
Thompson RP, Goebel J, Lindroth JR, Currie MG (1989) Embryology of the endocrine heart. In: Forssmann WG (ed) Functional morphology of the endocrine heart, Springer, Berlin Heidelberg New York, pp 1–11
Thompson RP, Lindroth JR, Alles A, Fazel AR (1990a) Cell differentiation birthdates in the embryonic rat heart. Proc NY Acad Sci 588:446–448
Thompson RP, Lindroth JR, Wong Y-MM (1990b) Regional differences in DNA-synthetic activity in the preseptation myocardium of the chick. In: Clark EB, Takao A (eds) Developmental cardiology: morphogenesis and function, Futura, Mt Kisco, NY, pp 219–234
Thorel C (1909) Vorläufige Mitteilung über eine besondere Muskelverbindung zwischen der Cava superior und dem His'schen Bündel. Munch Med Wschr 56:2159–2163
Tokuyasu KT (1990) Co-development of embryonic myocardium and myocardial circulation. In: Clark EB, Takao A (eds) Developmental cardiology: morphogenesis and function, Futura, Mt Kisco, NY, pp 205–218
Toshimori H, Toshimori K, Oura C, Matsuo H (1987) Immunohistochemical study of atrial natriuretic polypeptides in the embryonic, fetal, and neonatal rat heart. Cell Tissue Res 248:627–633
Truex RC, Marino TA, Marino DR (1978) Observations on the development of the human atrioventricular node and bundle. Anat Rec 192:337–350
Tucker GC, Aoyama M, Lipinski M, Tursz T, Thiery JP (1984) Identical activity of monoclonal antibodies HNK-1 and NC-1: conservation in vertebrates on cell derived from the neural primordium and on some leukocytes. Cell Differ 14:223–230
Van Mierop LHS, Gessner JH (1970) The morphologic development of the sinoatrial node in the mouse. Am J Cardiol 25:204–212
Vincent M, Thiery JP (1984) A cell surface marker for neural crest and placodal cells: further evolution of the peripheral and central nervous system. Dev Biol 103:468–481
Viragh S, Challice CE (1973) Origin and differentiation of cardiac muscle cells in the mouse. J Ultrastruct Res 42:1–24
Viragh S, Challice CE (1977) The development of the conduction system in the mouse embryo heart. II. Histogenesis of the atrio-ventricular node and bundle. Dev Biol 56:397–411
Viragh S, Challice CE (1980) The development of the conduction system in the mouse embryo heart. III. The development of sinus muscle and sinoatrial node. Dev Biol 80:28–45
Viragh S, Challice CE (1982) The development of the conduction system in the mouse embryo heart. IV. Differentiation of the atrioventricular conduction system. Dev Biol 89:25–40
Vitadello M, Matteoli M, Gorza L (1990) Neurofilament proteins are co-expressed with desmin in heart conduction system myocytes. J Cell Sci 97:11–21
Wenink ACG (1976) Development of the human cardiac conducting system. J Anat 121:617–631
Wessels A, Vermeulen JLM, Verbeek FJ, Viragh S, Kalman F, Lamers WH, Moorman AFM (1992) Spatial distribution of “tissue specific” antigens in the developing human heart and skeletal muscle. Anat Rec 232:97–111
Wharton J, Anderson RH, Springall D, Power RF, Rose M, Smith A, Espejo R, Khaghani A, Wallwork J, Yacoub M, Polak J (1988) Localisation of atrial natriuretic peptide immunoreactivity in the ventricular myocardium and conduction system of the human fetal and adult heart. Br Heart J 60:267–274
Wharton J, Gordon L, Walsh FS, Flanigan TP, Moore SE, Polak JM (1989) Neural cell adhesion molecule expression during cardiac development in the rat. Brain Res 483:170–176
Wong Y-MM, Thompson RP, Fitzharris TP (1983) Computer reconstruction of serial sections. Computer Biomed Res 16: 580–586
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Nakagawa, M., Thompson, R.P., Terracio, L. et al. Developmental anatomy of HNK-1 immunoreactivity in the embryonic rat heart: co-distribution with early conduction tissue. Anat Embryol 187, 445–460 (1993). https://doi.org/10.1007/BF00174420
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00174420