A tissue-specific, Gata6-driven transcriptional program instructs remodeling of the mature arterial tree

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.

Descrição

This deposit is composed by the main article plus the supplementary materials of the publication.

Palavras-chave

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

URI

http://hdl.handle.net/10400.7/789

Citação

eLife 2017;6:e31362 doi: 10.7554/eLife.31362

Editora

eLife Sciences Publications

DOI

10.7554/eLife.31362

Coleções

PM- Artigos

Licença CC

cclicense-by

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