UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Publication Date

9-27-2017

Document Type

Article

Disciplines

Cardiovascular Diseases | Cardiovascular System | Developmental Biology

Abstract

Connection of the heart to the systemic circulation is a critical developmental event that requires selective preservation of embryonic vessels (aortic arches). However, why some aortic arches regress while others are incorporated into the mature aortic tree remains unclear. By microdissection and deep sequencing in mouse, we find that neural crest (NC) only differentiates into vascular smooth muscle cells (SMCs) around those aortic arches destined for survival and reorganization, and identify the transcription factor Gata6 as a crucial regulator of this process. Gata6 is expressed in SMCs and its target genes activation control SMC differentiation. Furthermore, Gata6 is sufficient to promote SMCs differentiation in vivo, and drive preservation of aortic arches that ought to regress. These findings identify Gata6-directed differentiation of NC to SMCs as an essential mechanism that specifies the aortic tree, and provide a new framework for how mutations in GATA6 lead to congenital heart disorders in humans.

Keywords

developmental biology, embryo, great vessels, mouse, neural crest, smooth muscle cells, stem cells, transcription

Rights and Permissions

Copyright Losa et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

DOI of Published Version

10.7554/eLife.31362

Source

Elife. 2017 Sep 27;6. doi: 10.7554/eLife.31362. Link to article on publisher's site

Journal/Book/Conference Title

eLife

Related Resources

Link to Article in PubMed

PubMed ID

28952437

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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