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Molecular Pathways and Animal Models of Atrial Septal Defect

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Congenital Heart Diseases: The Broken Heart

Abstract

The seeming simplicity of the clinical presentation and management of an atrial septal defect belies the complexity of the developmental pathogenesis. Here, we describe the anatomic development of the atrial septum and the venous return to the atrial chambers. Recent experimental results suggest where genetic mutations could disrupt developmental steps to cause a defect within the oval fossa, the so-called secundum defect or other interatrial communication, such as the sinus venosus defect.

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References

  1. Anderson RH, Brown NA (1996) The anatomy of the heart revisited. Anat Rec 246:1–7

    Article  CAS  PubMed  Google Scholar 

  2. Rutland C, Warner L, Thorpe A et al (2009) Knockdown of alpha myosin heavy chain disrupts the cytoskeleton and leads to multiple defects during chick cardiogenesis. J Anat 214:905–915

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Jahr M, Manner J (2011) Development of the venous pole of the heart in the frog Xenopus laevis: a morphological study with special focus on the development of the venoatrial connections. Dev Dyn 240:1518–1527

    Article  PubMed  Google Scholar 

  4. Deniz E, Jonas S, Khokha M et al (2012) Endogenous contrast blood flow imaging in embryonic hearts using hemoglobin contrast subtraction angiography. Opt Lett 37:2979–2981

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Kelly RG (2012) The second heart field. Curr Top Dev Biol 100:33–65

    Article  CAS  PubMed  Google Scholar 

  6. Webb S, Brown NA, Anderson RH (1998) Formation of the atrioventricular septal structures in the normal mouse. Circ Res 82:645–656

    Article  CAS  PubMed  Google Scholar 

  7. Webb S, Kanani M, Anderson RH et al (2001) Development of the human pulmonary vein and its incorporation in the morphologically left atrium. Cardiol Young 11:632–642

    Article  CAS  PubMed  Google Scholar 

  8. Webb S, Brown NA, Wessels A et al (1998) Development of the murine pulmonary vein and its relationship to the embryonic venous sinus. Anat Rec 250:325–334

    Article  CAS  PubMed  Google Scholar 

  9. Mommersteeg MT, Soufan AT, de Lange FJ et al (2006) Two distinct pools of mesenchyme contribute to the development of the atrial septum. Circ Res 99:351–353

    Article  CAS  PubMed  Google Scholar 

  10. Snarr BS, O'Neal JL, Chintalapudi MR et al (2007) Isl1 expression at the venous pole identifies a novel role for the second heart field in cardiac development. Circ Res 101:971–974

    Article  CAS  PubMed  Google Scholar 

  11. Snarr BS, Wirrig EE, Phelps AL et al (2007) A spatiotemporal evaluation of the contribution of the dorsal mesenchymal protrusion to cardiac development. Dev Dyn 236:1287–1294

    Article  PubMed Central  PubMed  Google Scholar 

  12. Winston JB, Erlich JM, Green CA et al (2010) Heterogeneity of genetic modifiers ensures normal cardiac development. Circulation 121:1313–1321

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. van den Berg G, Moorman AF (2011) Development of the pulmonary vein and the systemic venous sinus: an interactive 3D overview. PLoS One 6, e22055

    Article  PubMed Central  PubMed  Google Scholar 

  14. Sizarov A, Anderson RH, Christoffels VM et al (2010) Three-dimensional and molecular analysis of the venous pole of the developing human heart. Circulation 122:798–807

    Article  PubMed  Google Scholar 

  15. Anderson RH, Mohun TJ, Brown NA (2015) Clarifying the morphology of the ostium primum defect. J Anat 226:244–257

    Article  PubMed  Google Scholar 

  16. Basson CT, Bachinsky DR, Lin RC et al (1997) Mutations in human TBX5 cause limb and cardiac malformation in Holt-Oram syndrome. Nat Genet 15:30–35

    Article  CAS  PubMed  Google Scholar 

  17. Li QY, Newbury-Ecob RA, Terrett JA et al (1997) Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family. Nat Genet 15:21–29

    Article  PubMed  Google Scholar 

  18. Bruneau BG, Logan M, Davis N et al (1999) Chamber-specific cardiac expression of Tbx5 and heart defects in Holt-Oram syndrome. Dev Biol 211:100–108

    Article  CAS  PubMed  Google Scholar 

  19. Bruneau BG, Nemer G, Schmitt JP et al (2001) A murine model of Holt-Oram syndrome defines roles of the T-box transcription factor Tbx5 in cardiogenesis and disease. Cell 106:709–721

    Article  CAS  PubMed  Google Scholar 

  20. Nadeau M, Georges RO, Laforest B et al (2010) An endocardial pathway involving Tbx5, Gata4, and Nos3 required for atrial septum formation. Proc Natl Acad Sci U S A 107:19356–19361

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Xie L, Hoffmann AD, Burnicka-Turek O et al (2012) Tbx5-hedgehog molecular networks are essential in the second heart field for atrial septation. Dev Cell 23:280–291

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Garg V, Kathiriya IS, Barnes R et al (2003) GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5. Nature 424:443–447

    Article  CAS  PubMed  Google Scholar 

  23. Jay PY, Bielinska M, Erlich JM et al (2007) Impaired mesenchymal cell function in Gata4 mutant mice leads to diaphragmatic hernias and primary lung defects. Dev Biol 301:602–614

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Rajagopal SK, Ma Q, Obler D et al (2007) Spectrum of heart disease associated with murine and human GATA4 mutation. J Mol Cell Cardiol 43:677–685

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Feng Q, Song W, Lu X et al (2002) Development of heart failure and congenital septal defects in mice lacking endothelial nitric oxide synthase. Circulation 106:873–879

    Article  CAS  PubMed  Google Scholar 

  26. Goddeeris MM, Rho S, Petiet A et al (2008) Intracardiac septation requires hedgehog-dependent cellular contributions from outside the heart. Development 135:1887–1895

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Hoffmann AD, Yang XH, Burnicka-Turek O et al (2014) Foxf genes integrate tbx5 and hedgehog pathways in the second heart field for cardiac septation. PLoS Genet 10, e1004604

    Article  PubMed Central  PubMed  Google Scholar 

  28. Bertrand N, Roux M, Ryckebusch L et al (2011) Hox genes define distinct progenitor sub-domains within the second heart field. Dev Biol 353:266–274

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Nguyen HH, Jay PY (2014) A single misstep in cardiac development explains the co-occurrence of tetralogy of fallot and complete atrioventricular septal defect in Down syndrome. J Pediatr 165:194–196

    Article  PubMed Central  PubMed  Google Scholar 

  30. Degenhardt K, Singh MK, Aghajanian H et al (2013) Semaphorin 3d signaling defects are associated with anomalous pulmonary venous connections. Nat Med 19:760–765

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. He Z, Wang KC, Koprivica V et al (2002) Knowing how to navigate: mechanisms of semaphorin signaling in the nervous system. Sci STKE 2002:re1

    PubMed  Google Scholar 

  32. Epstein JA, Aghajanian H, Singh MK (2015) Semaphorin signaling in cardiovascular development. Cell Metab 21:163–173

    Article  CAS  PubMed  Google Scholar 

  33. Cota CD, Bagher P, Pelc P et al (2006) Mice with mutations in Mahogunin ring finger-1 (Mgrn1) exhibit abnormal patterning of the left-right axis. Dev Dyn 235:3438–3447

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Patrick Y. Jay .

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© 2016 Springer-Verlag Wien

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Jay, P.Y., Degenhardt, K.R., Anderson, R.H. (2016). Molecular Pathways and Animal Models of Atrial Septal Defect. In: Rickert-Sperling, S., Kelly, R., Driscoll, D. (eds) Congenital Heart Diseases: The Broken Heart. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1883-2_21

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