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Lookup NU author(s): Dr Lu Wang, Dr Simon BamforthORCiD, Professor Bob Anderson
This is the authors' accepted manuscript of an article that has been published in its final definitive form by Oxford University Press, 2022.
For re-use rights please refer to the publisher's terms and conditions.
© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com. 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.
Author(s): Lin L, Pinto A, Wang L, Fukatsu K, Yin Y, Bamforth SD, Bronner ME, Evans SM, Nie S, Anderson RH, Terskikh AV, Grossfeld PD
Publication type: Article
Publication status: Published
Journal: Human Molecular Genetics
Year: 2022
Volume: 31
Issue: 24
Pages: 4217-4227
Print publication date: 15/12/2022
Online publication date: 28/07/2022
Acceptance date: 26/07/2022
Date deposited: 27/02/2023
ISSN (print): 0964-6906
ISSN (electronic): 1460-2083
Publisher: Oxford University Press
URL: https://doi.org/10.1093/hmg/ddac174
DOI: 10.1093/hmg/ddac174
ePrints DOI: 10.57711/ej79-vw79
PubMed id: 35899771
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