Toggle Main Menu Toggle Search

Open Access padlockePrints

ETS1 loss in mice impairs cardiac outflow tract septation via a cell migration defect autonomous to the neural crest

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: 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.

Publication metadata

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


DOI: 10.1093/hmg/ddac174

ePrints DOI: 10.57711/ej79-vw79

PubMed id: 35899771


Altmetrics provided by Altmetric


Funder referenceFunder name
11q Research and Resource Group
American Heart Association (#16GRNT26700008)
cast and crew of “How I Met Your Mother”
Chloe Duyck Memorial Fund
Hertz Family Foundation
Rady Children’s Hospital Foundation
Warren J. and Betty C. Zable Foundation