ETS1 loss in mice impairs cardiac outflow tract septation via a cell migration defect autonomous to the neural crest
Creators
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1.
University of California, San Diego
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2.
Newcastle University
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3.
California Institute of Technology
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4.
Georgia Institute of Technology
Abstract
Ets1 deletion in some mouse strains causes septal defects and has been implicated in human congenital heart defects in Jacobsen syndrome, in which one copy of the Ets1 gene is missing. Here, we demonstrate that loss of Ets1 in mice results in a decrease in neural crest (NC) cells migrating into the proximal outflow tract cushions during early heart development, with subsequent malalignment of the cushions relative to the muscular ventricular septum, resembling double outlet right ventricle (DORV) defects in humans. Consistent with this, we find that cultured cardiac NC cells from Ets1 mutant mice or derived from iPS cells from Jacobsen patients exhibit decreased migration speed and impaired cell-to-cell interactions. Together, our studies demonstrate a critical role for ETS1 for cell migration in cardiac NC cells that are required for proper formation of the proximal outflow tracts. These data provide further insights into the molecular and cellular basis for development of the outflow tracts, and how perturbation of NC cells can lead to DORV.
Additional Information
© The Author(s) 2022. Published by Oxford University Press. The authors would like to thank Dr Michael Ostrowski for providing the Ets1 floxed mice. The authors also would like to thank the UCSD School of Medicine Microscopy Core (Grant: NINDS P30 NS047101) for their invaluable technical support. Funding: American Heart Association (#16GRNT26700008); The Hertz Family Foundation; The Rady Children's Hospital Foundation; The 11q Research and Resource Group; The Chloe Duyck Memorial Fund; The Warren J. and Betty C. Zable Foundation and the cast and crew of 'How I Met Your Mother'. The authors have no disclosures.Attached Files
Published - ddac174.pdf
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Additional details
Identifiers
- PMCID
- PMC10148727
- Eprint ID
- 122534
- Resolver ID
- CaltechAUTHORS:20230725-706619000.50
Funding
- NIH
- P30 NS047101
- American Heart Association
- 16GRNT26700008
- Hertz Family Foundation
- Rady Children's Hospital Foundation
- 11q Research and Resource Group
- Chloe Duyck Memorial Fund
- Warren J. and Betty C. Zable Foundation
- How I Met Your Mother
Dates
- Created
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2023-08-13Created from EPrint's datestamp field
- Updated
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2023-08-14Created from EPrint's last_modified field