Mechanisms of Trabecular Formation and Specification During Cardiogenesis

Original Article

Abstract

Trabecular morphogenesis is a key morphologic event during cardiogenesis and contributes to the formation of a competent ventricular wall. Lack of trabeculation results in embryonic lethality. The trabecular morphogenesis is a multistep process that includes, but is not limited to, trabecular initiation, proliferation/growth, specification, and compaction. Although a number of signaling molecules have been implicated in regulating trabeculation, the cellular processes underlying mammalian trabecular formation are not fully understood. Recent works show that the myocardium displays polarity, and oriented cell division (OCD) and directional migration of the cardiomyocytes in the monolayer myocardium are required for trabecular initiation and formation. Furthermore, perpendicular OCD is an extrinsic asymmetric cell division that contributes to trabecular specification, and is a mechanism that causes the trabecular cardiomyocytes to be distinct from the cardiomyocytes in compact zone. Once the coronary vasculature system starts to function in the embryonic heart, the trabeculae will coalesce with the compact zone to thicken the heart wall, and abnormal compaction will lead to left ventricular non-compaction (LVNC) and heart failure. There are many reviews about compaction and LVNC. In this review, we will focus on the roles of myocardial polarity and OCD in trabecular initiation, formation, and specification.

Keywords

Myocardial polarity Oriented cell division Trabeculation Trabecular specification 

Notes

Acknowledgements

We thank the Wu laboratory members for scientific discussion, and Dr. John Schwarz for critical reading.

Compliance with Ethical Standards

Conflict of interest

The author declares that he has no competing interests.

Ethical Approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Research Involving Human Participants

This article does not contain any studies with human participants performed by any of the authors.

References

  1. 1.
    Manasek FJ (1968) Embryonic development of the heart. I. A light and electron microscopic study of myocardial development in the early chick embryo. J Morphol 125:329–365.  https://doi.org/10.1002/jmor.1051250306 CrossRefPubMedGoogle Scholar
  2. 2.
    Van Mierop LH (1979) Embryology of the univentricular heart. Herz 4:78–85PubMedGoogle Scholar
  3. 3.
    Sedmera D, Pexieder T, Vuillemin M, Thompson RP, Anderson RH (2000) Developmental patterning of the myocardium. Anat Rec 258:319–337CrossRefPubMedGoogle Scholar
  4. 4.
    Icardo JM, Fernandez-Teran A (1987) Morphologic study of ventricular trabeculation in the embryonic chick heart. Acta Anat 130:264–274CrossRefPubMedGoogle Scholar
  5. 5.
    Jenni R, Rojas J, Oechslin E (1999) Isolated noncompaction of the myocardium. N Engl J Med 340:966–967.  https://doi.org/10.1056/NEJM199903253401215 CrossRefPubMedGoogle Scholar
  6. 6.
    Gassmann M et al (1995) Aberrant neural and cardiac development in mice lacking the ErbB4 neuregulin receptor. Nature 378:390–394.  https://doi.org/10.1038/378390a0 CrossRefPubMedGoogle Scholar
  7. 7.
    Jefferies JL et al (2015) Cardiomyopathy phenotypes and outcomes for children with left ventricular myocardial noncompaction: results from the pediatric cardiomyopathy registry. J Cardiac Fail 21:877–884.  https://doi.org/10.1016/j.cardfail.2015.06.381 CrossRefGoogle Scholar
  8. 8.
    Towbin JA, Jefferies JL (2017) Cardiomyopathies due to left ventricular noncompaction, mitochondrial and storage diseases, and inborn errors of metabolism. Circ Res 121:838–854.  https://doi.org/10.1161/CIRCRESAHA.117.310987 CrossRefPubMedGoogle Scholar
  9. 9.
    Finsterer J (2010) Left ventricular non-compaction and its cardiac and neurologic implications. Heart Fail Rev 15:589–603.  https://doi.org/10.1007/s10741-010-9175-5 CrossRefPubMedGoogle Scholar
  10. 10.
    Hussein A, Karimianpour A, Collier P, Krasuski RA (2015) Isolated noncompaction of the left ventricle in adults. J Am Coll Cardiol 66:578–585.  https://doi.org/10.1016/j.jacc.2015.06.017 CrossRefPubMedGoogle Scholar
  11. 11.
    Weiford BC, Subbarao VD, Mulhern KM (2004) Noncompaction of the ventricular myocardium. Circulation 109:2965–2971.  https://doi.org/10.1161/01.CIR.0000132478.60674.D0 CrossRefPubMedGoogle Scholar
  12. 12.
    Horvitz HR, Herskowitz I (1992) Mechanisms of asymmetric cell division: two Bs or not two Bs, that is the question. Cell 68:237–255CrossRefPubMedGoogle Scholar
  13. 13.
    Jan YN, Jan LY (2000) Polarity in cell division: what frames thy fearful asymmetry?. Cell 100:599–602CrossRefPubMedGoogle Scholar
  14. 14.
    Neumuller RA, Knoblich JA (2009) Dividing cellular asymmetry: asymmetric cell division and its implications for stem cells and cancer. Genes Dev 23:2675–2699.  https://doi.org/10.1101/gad.1850809 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Wu M, Herman MA (2006) A novel noncanonical Wnt pathway is involved in the regulation of the asymmetric B cell division in C. elegans. Dev Biol 293:316–329.  https://doi.org/10.1016/j.ydbio.2005.12.024 CrossRefPubMedGoogle Scholar
  16. 16.
    Bryant DM, Mostov KE (2008) From cells to organs: building polarized tissue. Nat Rev Mol Cell Biol 9:887–901.  https://doi.org/10.1038/nrm2523 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Wu M et al (2010) Epicardial spindle orientation controls cell entry into the myocardium. Dev Cell 19:114–125.  https://doi.org/10.1016/j.devcel.2010.06.011 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Li J et al (2017) CDC42 is required for epicardial and pro-epicardial development by mediating FGF receptor trafficking to the plasma membrane. Development 144:1635–1647.  https://doi.org/10.1242/dev.147173 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Hirose T et al (2006) PAR3 is essential for cyst-mediated epicardial development by establishing apical cortical domains. Development 133:1389–1398.  https://doi.org/10.1242/dev.02294 CrossRefPubMedGoogle Scholar
  20. 20.
    Rhee DY et al (2009) Connexin 43 regulates epicardial cell polarity and migration in coronary vascular development. Development 136:3185–3193.  https://doi.org/10.1242/dev.032334 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Sengbusch JK, He W, Pinco KA, Yang JT (2002) Dual functions of α4β1 integrin in epicardial development: initial migration and long-term attachment. J Cell Biol 157:873–882.  https://doi.org/10.1083/jcb.200203075 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Jimenez-Amilburu V et al (2016) In vivo visualization of cardiomyocyte apicobasal polarity reveals epithelial to mesenchymal-like transition during cardiac trabeculation. Cell Rep 17:2687–2699.  https://doi.org/10.1016/j.celrep.2016.11.023 CrossRefPubMedGoogle Scholar
  23. 23.
    Passer D, van de Vrugt A, Atmanli A, Domian IJ (2016) Atypical protein kinase C-dependent polarized cell division is required for myocardial trabeculation. Cell Rep 14:1662–1672.  https://doi.org/10.1016/j.celrep.2016.01.030 CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Li J et al (2016) Single-cell lineage tracing reveals that oriented cell division contributes to trabecular morphogenesis and regional specification. Cell Rep 15:158–170.  https://doi.org/10.1016/j.celrep.2016.03.012 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Castanon I, Gonzalez-Gaitan M (2011) Oriented cell division in vertebrate embryogenesis. Curr Opin Cell Biol 23:697–704.  https://doi.org/10.1016/j.ceb.2011.09.009 CrossRefPubMedGoogle Scholar
  26. 26.
    Wei Y, Mikawa T (2000) Formation of the avian primitive streak from spatially restricted blastoderm: evidence for polarized cell division in the elongating streak. Development 127:87–96PubMedGoogle Scholar
  27. 27.
    Baena-Lopez LA, Baonza A, Garcia-Bellido A (2005) The orientation of cell divisions determines the shape of Drosophila organs. Curr Biol 15:1640–1644.  https://doi.org/10.1016/j.cub.2005.07.062 CrossRefPubMedGoogle Scholar
  28. 28.
    Liu J et al (2010) A dual role for ErbB2 signaling in cardiac trabeculation. Development 137:3867–3875.  https://doi.org/10.1242/dev.053736 CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Han P et al (2016) Coordinating cardiomyocyte interactions to direct ventricular chamber morphogenesis. Nature 534:700–704.  https://doi.org/10.1038/nature18310 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Staudt DW et al (2014) High-resolution imaging of cardiomyocyte behavior reveals two distinct steps in ventricular trabeculation. Development 141:585–593.  https://doi.org/10.1242/dev.098632 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Meilhac SM, Esner M, Kerszberg M, Moss JE, Buckingham ME (2004) Oriented clonal cell growth in the developing mouse myocardium underlies cardiac morphogenesis. J Cell Biol 164:97–109.  https://doi.org/10.1083/jcb.200309160 CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Meilhac SM, Esner M, Kelly RG, Nicolas JF, Buckingham ME (2004) The clonal origin of myocardial cells in different regions of the embryonic mouse heart. Dev Cell 6:685–698CrossRefPubMedGoogle Scholar
  33. 33.
    Meilhac SM et al (2003) A retrospective clonal analysis of the myocardium reveals two phases of clonal growth in the developing mouse heart. Development 130:3877–3889CrossRefPubMedGoogle Scholar
  34. 34.
    Mikawa T, Cohen-Gould L, Fischman DA (1992) Clonal analysis of cardiac morphogenesis in the chicken embryo using a replication-defective retrovirus. III: polyclonal origin of adjacent ventricular myocytes. Dev Dyn 195:133–141.  https://doi.org/10.1002/aja.1001950208 CrossRefPubMedGoogle Scholar
  35. 35.
    Du Q, Stukenberg PT, Macara IG (2001) A mammalian Partner of inscuteable binds NuMA and regulates mitotic spindle organization. Nat Cell Biol 3:1069–1075.  https://doi.org/10.1038/ncb1201-1069 CrossRefPubMedGoogle Scholar
  36. 36.
    Du Q, Macara IG (2004) Mammalian Pins is a conformational switch that links NuMA to heterotrimeric G proteins. Cell 119:503–516.  https://doi.org/10.1016/j.cell.2004.10.028 CrossRefPubMedGoogle Scholar
  37. 37.
    Mauser JF, Prehoda KE (2012) Inscuteable regulates the Pins-Mud spindle orientation pathway. PLoS ONE 7:e29611.  https://doi.org/10.1371/journal.pone.0029611 CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Laan L et al (2012) Cortical dynein controls microtubule dynamics to generate pulling forces that position microtubule asters. Cell 148:502–514.  https://doi.org/10.1016/j.cell.2012.01.007 CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Seldin L, Muroyama A, Lechler T (2016) NuMA-microtubule interactions are critical for spindle orientation and the morphogenesis of diverse epidermal structures. eLife.  https://doi.org/10.7554/eLife.12504 PubMedPubMedCentralGoogle Scholar
  40. 40.
    Hendricks AG et al (2012) Dynein tethers and stabilizes dynamic microtubule plus ends. Curr Biol 22:632–637.  https://doi.org/10.1016/j.cub.2012.02.023 CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Yap AS, Brieher WM, Gumbiner BM (1997) Molecular and functional analysis of cadherin-based adherens junctions. Annu Rev Cell Dev Biol 13:119–146.  https://doi.org/10.1146/annurev.cellbio.13.1.119 CrossRefPubMedGoogle Scholar
  42. 42.
    Inaba M, Yuan H, Salzmann V, Fuller MT, Yamashita YM (2010) E-cadherin is required for centrosome and spindle orientation in Drosophila male germline stem cells. PLoS ONE 5:e12473.  https://doi.org/10.1371/journal.pone.0012473 CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    den Elzen N, Buttery CV, Maddugoda MP, Ren G, Yap AS (2009) Cadherin adhesion receptors orient the mitotic spindle during symmetric cell division in mammalian epithelia. Mol Biol Cell 20:3740–3750.  https://doi.org/10.1091/mbc.E09-01-0023 CrossRefGoogle Scholar
  44. 44.
    Le Borgne R, Bellaiche Y, Schweisguth F (2002) Drosophila E-cadherin regulates the orientation of asymmetric cell division in the sensory organ lineage. Curr Biol 12:95–104 pii]CrossRefPubMedGoogle Scholar
  45. 45.
    Lu B, Roegiers F, Jan LY, Jan YN (2001) Adherens junctions inhibit asymmetric division in the Drosophila epithelium. Nature 409:522–525.  https://doi.org/10.1038/35054077 CrossRefPubMedGoogle Scholar
  46. 46.
    Yamashita YM, Jones DL, Fuller MT (2003) Orientation of asymmetric stem cell division by the APC tumor suppressor and centrosome. Science 301:1547–1550.  https://doi.org/10.1126/science.1087795 CrossRefPubMedGoogle Scholar
  47. 47.
    Gloerich M, Bianchini JM, Siemers KA, Cohen DJ, Nelson WJ (2017) Cell division orientation is coupled to cell–cell adhesion by the E-cadherin/LGN complex. Nat Commun 8:13996.  https://doi.org/10.1038/ncomms13996 CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Luo Y et al (2001) Rescuing the N-cadherin knockout by cardiac-specific expression of N- or E-cadherin. Development 128:459–469PubMedGoogle Scholar
  49. 49.
    Cherian AV, Fukuda R, Augustine SM, Maischein HM, Stainier DY (2016) N-cadherin relocalization during cardiac trabeculation. Proc Natl Acad Sci USA 113:7569–7574.  https://doi.org/10.1073/pnas.1606385113 CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Sedmera D et al (2003) Spatiotemporal pattern of commitment to slowed proliferation in the embryonic mouse heart indicates progressive differentiation of the cardiac conduction system. Anat Rec 274:773–777.  https://doi.org/10.1002/ar.a.10085 CrossRefGoogle Scholar
  51. 51.
    Zhang W, Chen H, Qu X, Chang CP, Shou W (2013) Molecular mechanism of ventricular trabeculation/compaction and the pathogenesis of the left ventricular noncompaction cardiomyopathy (LVNC). Am J Med Genet Part C 163:144–156.  https://doi.org/10.1002/ajmg.c.31369 CrossRefPubMedCentralGoogle Scholar
  52. 52.
    Kochilas LK, Li J, Jin F, Buck CA, Epstein JA (1999) p57Kip2 expression is enhanced during mid-cardiac murine development and is restricted to trabecular myocardium. Pediatr Res 45:635–642CrossRefPubMedGoogle Scholar
  53. 53.
    Chen H et al (2004) BMP10 is essential for maintaining cardiac growth during murine cardiogenesis. Development 131:2219–2231.  https://doi.org/10.1242/dev.01094 CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Clay H et al (2016) Sphingosine 1-phosphate receptor-1 in cardiomyocytes is required for normal cardiac development. Dev Biol 418:157–165.  https://doi.org/10.1016/j.ydbio.2016.06.024 CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Miao L et al (2018) Notch signaling regulates Hey2 expression in a spatiotemporal dependent manner during cardiac morphogenesis and trabecular specification. Sci Rep 8:2678.  https://doi.org/10.1038/s41598-018-20917-w CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Xin M et al (2007) Essential roles of the bHLH transcription factor Hrt2 in repression of atrial gene expression and maintenance of postnatal cardiac function. Proc Natl Acad Sci USA 104:7975–7980.  https://doi.org/10.1073/pnas.0702447104 CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Koibuchi N, Chin MT (2007) CHF1/Hey2 plays a pivotal role in left ventricular maturation through suppression of ectopic atrial gene expression. Circ Res 100:850–855.  https://doi.org/10.1161/01.RES.0000261693.13269.bf CrossRefPubMedGoogle Scholar
  58. 58.
    Kokubo H et al (2004) Targeted disruption of hesr2 results in atrioventricular valve anomalies that lead to heart dysfunction. Circ Res 95:540–547.  https://doi.org/10.1161/01.RES.0000141136.85194.f0 CrossRefPubMedGoogle Scholar
  59. 59.
    Lee KF et al (1995) Requirement for neuregulin receptor erbB2 in neural and cardiac development. Nature 378:394–398.  https://doi.org/10.1038/378394a0 CrossRefPubMedGoogle Scholar
  60. 60.
    Meyer D, Birchmeier C (1995) Multiple essential functions of neuregulin in development. Nature 378:386–390.  https://doi.org/10.1038/378386a0 CrossRefPubMedGoogle Scholar
  61. 61.
    Grego-Bessa J et al (2007) Notch signaling is essential for ventricular chamber development. Dev Cell 12:415–429.  https://doi.org/10.1016/j.devcel.2006.12.011 CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    VanDusen NJ et al (2014) Hand2 is an essential regulator for two Notch-dependent functions within the embryonic endocardium. Cell Rep 9:2071–2083.  https://doi.org/10.1016/j.celrep.2014.11.021 CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Xin M et al (2011) Regulation of insulin-like growth factor signaling by Yap governs cardiomyocyte proliferation and embryonic heart size. Sci Signal 4:ra70.  https://doi.org/10.1126/scisignal.2002278 CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    von Gise A et al (2012) YAP1, the nuclear target of Hippo signaling, stimulates heart growth through cardiomyocyte proliferation but not hypertrophy. Proc Natl Acad Sci USA 109:2394–2399.  https://doi.org/10.1073/pnas.1116136109 CrossRefGoogle Scholar
  65. 65.
    Li D et al (2011) Dishevelled-associated activator of morphogenesis 1 (Daam1) is required for heart morphogenesis. Development 138:303–315.  https://doi.org/10.1242/dev.055566 CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Zhao C et al (2014) Numb family proteins are essential for cardiac morphogenesis and progenitor differentiation. Development 141:281–295.  https://doi.org/10.1242/dev.093690 CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Wu M, Li J (2015) Numb family proteins: novel players in cardiac morphogenesis and cardiac progenitor cell differentiation. Biomol Concepts 6:137–148.  https://doi.org/10.1515/bmc-2015-0003 CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Tian X et al (2017) Identification of a hybrid myocardial zone in the mammalian heart after birth. Nat Commun 8:87.  https://doi.org/10.1038/s41467-017-00118-1 CrossRefPubMedPubMedCentralGoogle Scholar

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Authors and Affiliations

  1. 1.Department of Molecular and Cellular PhysiologyAlbany Medical CollegeAlbanyUSA

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