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

Author:

Lin Lizhu1,Pinto Antonella2,Wang Lu1,Fukatsu Kazumi1,Yin Yan1,Bamforth Simon D3,Bronner Marianne E4,Evans Sylvia M5,Nie Shuyi6,Anderson Robert H3,Terskikh Alexey V2,Grossfeld Paul D17ORCID

Affiliation:

1. Department of Pediatrics, UCSD School of Medicine , La Jolla, CA 92093 , USA

2. Department of Biology, Sanford-Burnham-Prebys Institute of Medical Discovery , La Jolla, CA 92037 , USA

3. Cardiovascular Research Centre, Institute of Genetic Medicine, Newcastle University , Newcastle upon Tyne NE1 3BZ , UK

4. Department of Biology, California Institute of Technology , Pasadena, CA 91125 , USA

5. Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, UCSD , La Jolla, CA 92093 , USA

6. Department of Biology, Georgia Institute of Technology , Atlanta, GA 30332 , USA

7. Division of Cardiology, Rady Children’s Hospital , San Diego, CA 92123 , USA

Abstract

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.

Funder

American Heart Association

Hertz Family Foundation

Rady Children’s Hospital Foundation

11q Research and Resource Group

Chloe Duyck Memorial Fund

NIH

Publisher

Oxford University Press (OUP)

Subject

Genetics (clinical),Genetics,Molecular Biology,General Medicine

Cited by 3 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3