The embryonic epicardium and the cardiac mesenchyme derived from it are critical to heart development. The embryonic epicardium arises from an extracardiac progenitor tissue called the proepicardium, a proliferation of coelomic cells located at the limit between the liver and the sinus venosus. A proepicardium has not been described in invertebrates, and the evolutionary origin of this structure in vertebrates is unknown. We herein suggest that the proepicardium might be regarded as an evolutionary derivative from an ancient pronephric external glomerulus that has lost its excretory role. In fact, we previously described that the epicardium arises by cell migration from the primordia of the right pronephric external glomerulus in a representative of the most primitive vertebrate lineage, the lamprey Petromyzon marinus. In this review, we emphasize the striking similarities between the gene expression profiles of the proepicardium and the developing kidneys, as well as the parallelisms in the signaling mechanisms involved in both cases. We show some preliminary evidence about the existence of an inhibitory mechanism blocking glomerular differentiation in the proepicardium. We speculate as to the possibility that this developmental link between heart and kidney can be revealing a phylogenetically deeper association, supported by the existence of a heart-kidney complex in Hemichordates. Finally, we suggest that primitive hematopoiesis could be related with this heart-kidney complex, thus accounting for the current anatomical association of the hematopoietic stem cells with an aorta-gonad-mesonephros area. In summary, we think that our hypothesis can provide new perspectives on the evolutionary origin of the vertebrate heart.
References
[1]
Manasek, F.J. Embryonic development of the heart. I. A light and electron microscopic study of myocardial development in the early chick embryo. J. Morphol. 1968, 125, 329–365, doi:10.1002/jmor.1051250306.
[2]
Manasek, F.J. Embryonic development of the heart. II. Formation of the epicardium. J. Embryol. Exp. Morphol. 1969, 22, 333–348.
[3]
His, W. Anatomie menschlicher Embryonen. Teil III Zur Geschichte der Organe; Vogel: Leipzig, Germany, 1885.
[4]
Kurkiewicz, T. O histogenezie miesna sercowego zwierzat kregowych - Zur Histogenese des Herzmuskels der Wirbeltiere. Bul. Int. Acad. Sci. Cracovie 1909, 177, 148–191.
[5]
M？nner, J.; Pérez-Pomares, J.M.; Macías, D.; Mu？oz-Chápuli, R. The origin, formation, and developmental significance of the epicardium: a review. Cell Tiss. Org. 2001, 169, 89–103, doi:10.1159/000047867.
[6]
Budelmann, B.U.; Schipp, R.; Von Boletzky, S. Cephalopoda. In Microscopic Anatomy of Invertebrates; Harrison, F.W., Kohn, A.J., Eds.; Wiley-Liss: New York, NY, USA, 1997; Volume 6A, pp. 119–414.
[7]
Pombal, M.A.; Carmona, R.; Megías, M.; Ruiz, A.; Pérez-Pomares, J.M.; Mu？oz-Chápuli, R. Epicardial development in lamprey supports an evolutionary origin of the vertebrate epicardium from an ancestral pronephric external glomerulus. Evol. Dev. 2008, 10, 210–216, doi:10.1111/j.1525-142X.2008.00228.x.
[8]
Jahr, M.; Schlueter, J.; Brand, T.; M？nner, J. Development of the proepicardium in Xenopus laevis. Dev. Dyn. 2008, 237, 3088–3096, doi:10.1002/dvdy.21713.
[9]
Schlueter, J.; Brand, T. A right-sided pathway involving FGF8/Snai1 controls asymmetric development of the proepicardium in the chick embryo. Proc. Natl. Acad. Sci. USA 2009, 106, 7485–7490, doi:10.1073/pnas.0811944106.
[10]
Schulte, I.; Schlueter, J.; Abu-Issa, R.; Brand, T.; Manner, J. Morphological and molecular left-right asymmetries in the development of the proepicardium: A comparative analysis on mouse and chick embryos. Dev. Dyn. 2007, 236, 684–695, doi:10.1002/dvdy.21065.
[11]
Mu？oz-Chápuli, R.; Macías, D.; Ramos, C.; De Andrés, A.V.; Gallego, A.; Navarro, P. Heart development in the dogfish (Scyliorhinus canicula): A model for the study of the basic vertebrate cardiogenesis. Cardioscience 1994, 5, 245–253.
[12]
Mu？oz-Chápuli, R.; Macías, D.; Ramos, C.; Fernández, B.; Sans-Coma, V. Development of the epicardium in the dogfish (Scyliorhinus canicula). Acta Zool. 1997, 78, 39–46, doi:10.1111/j.1463-6395.1997.tb01124.x.
[13]
Icardo, J.M.; Guerrero, A.; Durán, A.C.; Colvee, E.; Domezain, A.; Sans-Coma, V. The development of the epicardium in the sturgeon Acipenser naccarii. Anat. Rec. 2009, 292, 1593–1601, doi:10.1002/ar.20939.
[14]
Serluca, F.C. Development of the proepicardial organ in the zebrafish. Dev. Biol. 2008, 315, 18–27, doi:10.1016/j.ydbio.2007.10.007.
[15]
Fransen, M.E.; Lemanski, L.F. Epicardial development in the axolotl, Ambystoma mexicanum. Anat. Rec. 1990, 226, 228–236, doi:10.1002/ar.1092260212.
[16]
Sejima, H.; Isokawa, K.; Shimizu, O.; Morikawa, T.; Ootsu, H.; Numata, K.; Fukai, M.; Kubota, S.; Toda, Y. Possible participation of isolated epicardial cell clusters in the formation of chick embryonic epicardium. J. Oral Sci. 2001, 43, 109–106, doi:10.2334/josnusd.43.109.
[17]
Komiyama, M.; Ito, K.; Shimada, Y. Origin and development of the epicardium in the mouse embryo. Anat. Embryol. 1987, 176, 183–189, doi:10.1007/BF00310051.
[18]
Kuhn, H.J.; Liebherr, G. The early development of the epicardium in Tupaja belangerie. Anat. Embryol. 1988, 177, 225–234, doi:10.1007/BF00321133.
[19]
M？nner, J. The development of pericardial villi in the chick embryo. Anat. Embryol. 1992, 186, 379–385, doi:10.1007/BF00185988.
[20]
M？nner, J. Experimental study on the formation of the epicardium in chick embryos. Anat Embryol. 1993, 187, 281–289, doi:10.1007/BF00195766.
[21]
MacKinnon, M.R.; Heatwole, H. Comparative cardiac anatomy of the reptilia. IV. The coronary arterial circulation. J. Morphol. 1981, 170, 1–27, doi:10.1002/jmor.1051700102.
[22]
Davies, F.; Francis, E.T.B.; King, T.S. The conducting (connecting) system of the crocodilian heart. J. Anat. 1952, 86, 152–161.
[23]
Buchanan, J.G. The Gross and Minute Anatomy of the Heart of the Lizard, Leiolopisma grande (Gray). Trans. Proc. Royal Soc. N. Z. 1956, 84, 103–119.
[24]
Viragh, S.; Gittenberger-de Groot, A.C.; Poelmann, R.E.; Kalman, F. Early development of quail heart epicardium and associated vascular and glandular structures. Anat. Embryol. 1993, 188, 381–393.
[25]
Virágh, S.; Challice, C.E. The origin of the epicardium and the embryonic myocardial circulation in the mouse. Anat. Rec. 1981, 201, 157–168, doi:10.1002/ar.1092010117.
[26]
Brandli, A.W. Towards a molecular anatomy of the Xenopus pronephric kidney. Int. J. Dev. Biol. 1999, 43, 381–395.
[27]
Jones, E.A. Xenopus: A prince among models for pronephric kidney development. J. Am. Soc. Nephrol. 2005, 16, 313–321, doi:10.1681/ASN.2004070617.
[28]
Hiruma, T.; Nakamura, H. Origin and development of the pronephros in the chick embryo. J. Anat. 2003, 203, 539–552, doi:10.1046/j.1469-7580.2003.00245.x.
[29]
Stuckmann, I.; Evans, S.; Lassar, A.B. Erythropoietin and retinoic acid, secreted from the epicardium, are required for cardiac myocyte proliferation. Dev. Biol. 2003, 255, 334–349, doi:10.1016/S0012-1606(02)00078-7.
Merki, E.; Zamora, M.; Raya, A.; Kawakami, Y.; Wang, J.; Zhang, X.; Burch, J.; Kubalak, S.W.; Kaliman, P.; Izpisúa-Belmonte, J.C.; Chien, K.R.; Ruiz-Lozano, P. Epicardial retinoid X receptor alpha is required for myocardial growth and coronary artery formation. Proc. Natl. Acad. Sci. USA 2005, 102, 18455–18460, doi:10.1073/pnas.0504343102.
[32]
Martínez-Estrada, O.M.; Lettice, L.A.; Essafi, A.; Guadix, J.A.; Slight, J.; Velecela, V.; Hall, E.; Reichmann, J.; Devenney, P.S.; Hohenstein, P.; Hosen, N.; Hill, R.E.; Mu？oz-Chapuli, R.; Hastie, N.D. Wt1 is required for mesenchymal cardiovascular progenitor cell formation in epicardium and ES cells through direct transcriptional control of Snail and E-cadherin. Nat. Genet. 2010, 42, 89–93, doi:10.1038/ng.494.
[33]
Drummond, I.A.; Majumdar, A.; Hentschel, H.; Elger, M.; Solnica-Krezel, L.; Schier, A.F.; Neuhauss, S.C.; Stemple, D.L.; Zwartkruis, F.; Rangini, Z.; Driever, W.; Fishman, M.C. Early development of the zebrafish pronephros and analysis of mutations affecting pronephric function. Development 1998, 125, 4655–4667.
[34]
Moore, A.W.; McInnes, L.; Kreidberg, J.; Hastie, N.D.; Schedl, A. YAC complementation shows a requirement for Wt1 in the development of epicardium, adrenal gland and throughout nephrogenesis. Development 1999, 126, 1845–1857.
[35]
Quaggin, S.E.; Schwartz, L.; Cui, S.; Igarashi, P.; Deimling, J.; Post, M.; Rossant, J. The basic-helix-loop-helix protein pod1 is critically important for kidney and lung organogenesis. Development 1999, 126, 5771–5783.
[36]
Cui, S.; Schwartz, L.; Quaggin, S.E. Pod1 is required in stromal cells for glomerulogenesis. Dev. Dyn. 2003, 226, 512–522, doi:10.1002/dvdy.10244.
[37]
Acharya, A.; Baek, S.T.; Huang, G.; Eskiocak, B.; Goetsch, S.; Sung, C.Y.; Banfi, S.; Sauer, M.F.; Olsen, G.S.; Duffield, J.S.; Olson, E.N.; Tallquist, M.D. The bHLH transcription factor Tcf21 is required for lineage-specific EMT of cardiac fibroblast progenitors. Development 2012, 139, 2139–2149, doi:10.1242/dev.079970.
[38]
Christoffels, V.M.; Mommersteeg, M.T.; Trowe, M.O.; Prall, O.W.; de Gier-de Vries, C.; Soufan, A.T.; Bussen, M.; Schuster-Gossler, K.; Harvey, R.P.; Moorman, A.F.; 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, doi:10.1161/01.RES.0000227571.84189.65.
[39]
Takeichi, M.; Nimura, K.; Mori, M.; Nakagami, H.; Kaneda, Y. The transcription factors Tbx18 and Wt1 control the epicardial epithelial-mesenchymal transition through bi-directional regulation of Slug in murine primary epicardial cells. PLoS One 2013, 8, e57829.
[40]
Putaala, H.; Soininen, R.; Kilpelainen, P.; Wartiovaara, J.; Tryggvason, K. The murine nephrin gene is specifically expressed in kidney, brain and pancreas: inactivation of the gene leads to massive proteinuria and neonatal death. Hum. Mol. Genet. 2001, 10, 1–8, doi:10.1093/hmg/10.1.1.
[41]
Wagner, N.; Morrison, H.; Pagnotta, S.; Michiels, J.F.; Schwab, Y.; Tryggvason, K.; Schedl, A.; Wagner, K.D. The podocyte protein nephrin is required for cardiac vessel formation. Hum. Mol. Genet. 2011, 20, 2182–2194, doi:10.1093/hmg/ddr106.
[42]
Wagner, N.; Wagner, K.D.; Scholz, H.; Kirschner, K.M.; Schedl, A. Intermediate filament protein nestin is expressed in developing kidney and heart and might be regulated by the Wilms' tumor suppressor Wt1. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2006, 291, R779–R787, doi:10.1152/ajpregu.00219.2006.
[43]
Wharram, B.L.; Goyal, M.; Gillespie, P.J.; Wiggins, J.E.; Kershaw, D.B.; Holzman, L.B.; Dysko, R.C.; Saunders, T.L.; Samuelson, L.C.; Wiggins, R.C. Altered podocyte structure in GLEPP1 (Ptpro)-deficient mice associated with hypertension and low glomerular filtration rate. J. Clin. Invest. 2000, 106, 1281–1290, doi:10.1172/JCI7236.
[44]
Osafune, K.; Nishinakamura, R.; Komazaki, S.; Asashima, M. In vitro induction of the pronephric duct in Xenopus explants. Develop. Growth Differ. 2002, 44, 161–167, doi:10.1046/j.1440-169x.2002.00631.x.
Jenkins, S.J.; Hutson, D.R.; Kubalak, S.W. Analysis of the proepicardium-epicardium transition during the malformation of the RXRalpha-/- epicardium. Dev. Dyn. 2005, 233, 1091–1101, doi:10.1002/dvdy.20393.
[47]
Vaughan, M.R.; Pippin, J.W.; Griffin, S.V.; Krofft, R.; Fleet, M.; Haseley, L.; Shankland, S.J. ATRA induces podocyte differentiation and alters nephrin and podocin expression in vitro and in vivo. Kidney Int. 2005, 68, 133–144, doi:10.1111/j.1523-1755.2005.00387.x.
Bouchard, M.; Souabni, A.; Mandler, M.; Neubüser, A.; Busslinger, M. Nephric lineage specification by Pax2 and Pax8. Genes Dev. 2002, 16, 2958–2970, doi:10.1101/gad.240102.
[50]
Torban, E.; Dziarmaga, A.; Iglesias, D.; Chu, L.L.; Vassilieva, T.; Little, M.; Eccles, M.; Discenza, M.; Pelletier, J.; Goodyer, P. PAX2 activates WNT4 expression during mammalian kidney development. J. Biol. Chem. 2006, 281, 12705–12712, doi:10.1074/jbc.M513181200.
[51]
Dressler, G.R. Patterning and early cell lineage decisions in the developing kidney: The role of Pax genes. Pediatr. Nephrol. 2011, 26, 1387–1394, doi:10.1007/s00467-010-1749-x.
[52]
Phelps, D.E.; Dressler, G.R. Aberrant expression of Pax2 in Danforth's short tail (Sd) mice. Dev. Biol. 1993, 157, 251–258, doi:10.1006/dbio.1993.1129.
[53]
Ryan, G.; Steele-Perkins, V.; Morris, J.F.; Rauscher, F.J., 3rd; Dressler, G.R. Repression of Pax2 by WT1 during normal kidney development. Development 1995, 121, 867–875.
[54]
Watt, A.J.; Battle, M.A.; Li, J.; Duncan, S.A. GATA4 is essential for formation of the proepicardium and regulates cardiogenesis. Proc. Natl. Acad. Sci. USA 2004, 101, 12573–12578.
[55]
Dame, C.; Sola, M.C.; Lim, K.C.; Leach, K.M.; Fandrey, J.; Ma, Y.; Kn？pfle, G.; Engel, J.D.; Bungert, J. Hepatic erythropoietin gene regulation by GATA-4. J. Biol. Chem. 2004, 279, 2955–2961.
[56]
Zhou, B.; von Gise, A.; Ma, Q.; Rivera-Feliciano, J.; Pu, W.T. Nkx2–5- and Isl1-expressing cardiac progenitors contribute to proepicardium. Biochem. Biophys. Res. Commun. 2008, 375, 450–453, doi:10.1016/j.bbrc.2008.08.044.
[57]
Holmgren, N. On the pronephros and the blood in Myxine glutinosa. Acta Zool. 1950, 31, 233–348, doi:10.1111/j.1463-6395.1950.tb00514.x.
[58]
F？nge, R. Structure and function of the excretory organs of Myxinoids. In The Biology of Myxine; Brodal, A., F？nge, R., Eds.; Universitetforlaget: Oslo, Norway, 1963; pp. 516–529.
[59]
Lowe, C.J.; Terasaki, M.; Wu, M.; Freeman, R.M., Jr.; Runft, L.; Kwan, K.; Haigo, S.; Aronowicz, J.; Lander, E.; Gruber, C.; Smith, M.; Kirschner, M.; Gerhart, J. Dorsoventral patterning in hemichordates: insights into early chordate evolution. PLoS Biol. 2006, 4, e291, doi:10.1371/journal.pbio.0040291.
[60]
Pascual-Anaya, J.; Albuixech-Crespo, B.; Somorjai, I.M.; Carmona, R.; Oisi, Y.; Alvarez, S.; Kuratani, S.; Mu？oz-Chápuli, R.; Garcia-Fernández, J. The evolutionary origins of chordate hematopoiesis and vertebrate endothelia. Dev. Biol. 2013, 375, 182–192, doi:10.1016/j.ydbio.2012.11.015.
[61]
Hirakow, R. Epicardial formation in staged human embryos. Acta Anat. Nippon. 1992, 67, 616–622.
[62]
Kattan, J.; Dettman, R.W.; Bristow, J. Formation and remodeling of the coronary vascular bed in the embryonic avian heart. Dev. Dyn. 2004, 230, 34–43, doi:10.1002/dvdy.20022.
[63]
Tomanek, R.J.; Ishii, Y.; Holifield, J.S.; Sjogren, C.L.; Hansen, H.K.; Mikawa, T. VEGF family members regulate myocardial tubulogenesis and coronary artery formation in the embryo. Circ. Res. 2006, 98, 947–953, doi:10.1161/01.RES.0000216974.75994.da.
[64]
Wilting, J.; Buttler, K.; Schulte, I.; Papoutsi, M.; Schweigerer, L.; Manner, J. The proepicardium delivers hemangioblasts but not lymphangioblasts to the developing heart. Dev. Biol. 2007, 305, 451–459, doi:10.1016/j.ydbio.2007.02.026.
[65]
Carpenter, K.L.; Turpen, J.B. Experimental studies on hemopoiesis in the pronephros of Rana pipiens. Differentiation 1979, 14, 167–174, doi:10.1111/j.1432-0436.1979.tb01025.x.
[66]
Willett, C.E.; Cortés, A.; Zuasti, A.; Zapata, A.G. Early hematopoiesis and developing lymphoid organs in the zebrafish. Dev. Dyn. 1999, 214, 323–336, doi:10.1002/(SICI)1097-0177(199904)214:4<323::AID-AJA5>3.0.CO;2-3.
[67]
Luchtel, L.L.; Martin, A.W.; Deyrup-Olsen, I.; Boer, H.H. Gastropoda: Pulmonata. In Microscopic Anatomy of Invertebrates; Harrison, F.W., Kohn, A.J., Eds.; Wiley-Liss: New York, NY, USA, 1997; Volume 6B, pp. 459–718.
[68]
？kland, S. The heart ultrastructure of Lepidopleurus asellus (Spengler) and Tonicella marmorea (Fabricius) (Mollusca: Polyplacophora). Zoomorphology 1980, 96, 1–19, doi:10.1007/BF00310073.
[69]
Fahrner, A.; Haszprunar, G. Microanatomy, ultrastructure, and systematic significance of the excretory system and mantle cavity of an acochlidian gastropod (Opisthobranchia). J. Moll. Stud. 2002, 68, 87–94, doi:10.1093/mollus/68.1.87.
[70]
Denholm, B.; Skaer, H. Bringing together components of the fly renal system. Curr. Opin. Genet. Dev. 2009, 19, 526–532, doi:10.1016/j.gde.2009.08.006.
[71]
Mandal, L.; Banerjee, U.; Hartenstein, V. Evidence for a fruit fly hemangioblast and similarities between lymph-gland hematopoiesis in fruit fly and mammal aorta-gonadal-mesonephros mesoderm. Nat. Genet. 2004, 36, 1019–1023, doi:10.1038/ng1404.
[72]
Ishii, Y.; Langberg, J.D.; Hurtado, R.; Lee, S.; Mikawa, T. Induction of proepicardial marker gene expression by the liver bud. Development 2007, 134, 3627–3637, doi:10.1242/dev.005280.
[73]
Liu, J.; Stainier, D.Y. Tbx5 and Bmp signaling are essential for proepicardium specification in zebrafish. Circ. Res. 2010, 106, 1818–1828, doi:10.1161/CIRCRESAHA.110.217950.
[74]
Wagner, K.D.; Wagner, N.; Bondke, A.; Nafz, B.; Flemming, B.; Theres, H.; Scholz, H. The Wilms' tumor suppressor Wt1 is expressed in the coronary vasculature after myocardial infarction. FASEB J. 2002, 16, 1117–1119.
