Biomechanical signaling within the developing zebrafish heart attunes endocardial growth to myocardial chamber dimensions

Nat Commun. 2019 Sep 11;10(1):4113. doi: 10.1038/s41467-019-12068-x.

Abstract

Intra-organ communication guides morphogenetic processes that are essential for an organ to carry out complex physiological functions. In the heart, the growth of the myocardium is tightly coupled to that of the endocardium, a specialized endothelial tissue that lines its interior. Several molecular pathways have been implicated in the communication between these tissues including secreted factors, components of the extracellular matrix, or proteins involved in cell-cell communication. Yet, it is unknown how the growth of the endocardium is coordinated with that of the myocardium. Here, we show that an increased expansion of the myocardial atrial chamber volume generates higher junctional forces within endocardial cells. This leads to biomechanical signaling involving VE-cadherin, triggering nuclear localization of the Hippo pathway transcriptional regulator Yap1 and endocardial proliferation. Our work suggests that the growth of the endocardium results from myocardial chamber volume expansion and ends when the tension on the tissue is relaxed.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Biomechanical Phenomena
  • Cadherins / metabolism
  • Cell Nucleus / metabolism
  • Cell Proliferation
  • Cell Size
  • Cytoskeletal Proteins / metabolism
  • Endocardium / cytology
  • Endocardium / growth & development*
  • Heart Atria / cytology
  • Heart Atria / metabolism
  • Homeobox Protein Nkx-2.5 / metabolism
  • Intercellular Junctions / metabolism
  • Models, Biological
  • Mutation / genetics
  • Myocardium / metabolism*
  • Signal Transduction*
  • Trans-Activators / metabolism
  • Wnt Proteins / metabolism
  • Zebrafish / embryology*
  • Zebrafish Proteins / metabolism

Substances

  • Antigens, CD
  • Cadherins
  • Cytoskeletal Proteins
  • Homeobox Protein Nkx-2.5
  • Trans-Activators
  • Wnt Proteins
  • Yes-associated protein (yap), zebrafish
  • Zebrafish Proteins
  • cadherin 5
  • wnt8a protein, zebrafish