PUBLICATION

Cardiac function modulates endocardial cell dynamics to shape the cardiac outflow tract

Authors
Sidhwani, P., Leerberg, D.M., Boezio, G.L.M., Capasso, T.L., Yang, H., Chi, N.C., Roman, B.L., Stainier, D.Y.R., Yelon, D.
ID
ZDB-PUB-200524-4
Date
2020
Source
Development (Cambridge, England)   147(12): (Journal)
Registered Authors
Chi, Neil C., Leerberg, Dena M., Roman, Beth, Stainier, Didier, Yang, Hongbo, Yelon, Deborah
Keywords
Acvrl1, Cardiac function, Endocardium, Heart development, Outflow tract, Zebrafish
MeSH Terms
  • Animals
  • Troponin T/antagonists & inhibitors
  • Troponin T/genetics
  • Troponin T/metabolism
  • Endocardium/cytology
  • Endocardium/metabolism*
  • Zebrafish Proteins/antagonists & inhibitors
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Cell Proliferation
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/metabolism
  • Animals, Genetically Modified/growth & development
  • Animals, Genetically Modified/metabolism
  • Heart/anatomy & histology
  • Heart/growth & development
  • Heart/physiology*
  • Zebrafish/growth & development
  • Zebrafish/metabolism*
  • Morpholinos/metabolism
  • Activin Receptors/antagonists & inhibitors
  • Activin Receptors/genetics
  • Activin Receptors/metabolism
(all 23)
PubMed
32439760 Full text @ Development
Abstract
Physical forces are important participants in the cellular dynamics that shape developing organs. During heart formation, for example, contractility and blood flow generate biomechanical cues that influence patterns of cell behavior. Here, we address the interplay between function and form during the assembly of the cardiac outflow tract (OFT), a crucial connection between the heart and vasculature that develops while circulation is underway. In zebrafish, we find that the OFT expands via accrual of both endocardial and myocardial cells. However, when cardiac function is disrupted, OFT endocardial growth ceases, accompanied by reduced proliferation and reduced addition of cells from adjacent vessels. The flow-responsive TGFβ receptor Acvrl1 is required for addition of endocardial cells, but not for their proliferation, indicating distinct modes of function-dependent regulation for each of these essential cell behaviors. Together, our results indicate that cardiac function modulates OFT morphogenesis by triggering endocardial cell accumulation that induces OFT lumen expansion and shapes OFT dimensions; moreover, these morphogenetic mechanisms provide new perspectives regarding the potential causes of cardiac birth defects.
Genes / Markers
Figures
Figure Gallery (8 images)
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Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
b109
    		Small Deletion
    bns11
      		Small Deletion
      ft09e
        		Point Mutation
        is4TgTransgenic Insertion
          la116TgTransgenic Insertion
            m58
              		Small Deletion
              pt516TgTransgenic Insertion
                s896TgTransgenic Insertion
                  sd8TgTransgenic Insertion
                    sd12TgTransgenic Insertion
                      1 - 10 of 14
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                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      Target Reagent Reagent Type
                      acvrl1MO3-acvrl1MRPHLNO
                      myh6MO1-myh6MRPHLNO
                      tnnt2aMO1-tnnt2aMRPHLNO
                      1 - 3 of 3
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                      Fish
                      No data available
                      Antibodies
                      Orthology
                      No data available
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      DendraEFGDendra
                      EGFPEFGEGFP
                      GFPEFGGFP
                      grcfpEFGgrcfp
                      mCherryEFGmCherry
                      1 - 5 of 5
                      Show
                      Mapping
                      No data available
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                      Citation
                      Sidhwani, P., Leerberg, D.M., Boezio, G.L.M., Capasso, T.L., Yang, H., Chi, N.C., Roman, B.L., Stainier, D.Y.R., Yelon, D. (2020) Cardiac function modulates endocardial cell dynamics to shape the cardiac outflow tract. Development (Cambridge, England). 147(12):.