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

Pragya Sidhwani; Dena M. Leerberg; Giulia L.M. Boezio; Teresa L. Capasso; Hongbo Yang; Neil C. Chi; Beth L. Roman; Didier Y.R. Stainier; Deborah Yelon

doi:10.1242/dev.185900

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

Pragya Sidhwani, Dena M. Leerberg, Giulia L.M. Boezio, Teresa L. Capasso, Hongbo Yang, Neil C. Chi, Beth L. Roman, Didier Y.R. Stainier, Deborah Yelon^*

^*Corresponding author for this work

Biochemistry and Molecular Genetics

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

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 under way. 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.

Original language	English (US)
Article number	dev185900
Journal	Development (Cambridge)
Volume	147
Issue number	12
DOIs	https://doi.org/10.1242/dev.185900
State	Published - Jun 17 2020

Funding

We are grateful for helpful discussions with K. Cooper, X. Sun, J. Posakony, A. Chisholm, E. M. Collins and members of the Yelon lab; for expert zebrafish care by T. Sanchez and H. Kwan; for reagents, advice and assistance provided by A. Anbalagan, S. J. Rasouli and I. G. Chu; and for light-sheet microscopy assistance from J. Santini and M. Erb. The University of California, San Diego, School of Medicine Microscopy Core Facility is supported by the National Institutes of Health (P30 NS047101). This work was supported by grants to D.Y. from the National Institutes of Health [R01 HL108599 and R01 OD026219], to D.M.L. from the American Heart Association [20POST35110077], to N.C.C. from the National Institutes of Health, to B.L.R. from the National Institutes of Health [R01 HL136566, P30 NS047101 and R01 HL133009], and to D.Y.R.S. from the Max-Planck-Gesellschaft, Deutsche Forschungsgemeinschaft, European Research Council (ERC AdG project ZMOD 694455) and Fondation Leducq. Deposited in PMC for release after 12 months.

Keywords

Acvrl1
Cardiac function
Endocardium
Heart development
Outflow tract
Zebrafish

ASJC Scopus subject areas

Molecular Biology
Developmental Biology

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10.1242/dev.185900

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title = "Cardiac function modulates endocardial cell dynamics to shape the cardiac outflow tract",

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 under way. 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.",

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AU - Yang, Hongbo

AU - Chi, Neil C.

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AU - Stainier, Didier Y.R.

AU - Yelon, Deborah

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

Abstract

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Keywords

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