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

First Author  Losa M Year  2017
Journal  Elife Volume  6
PubMed ID  28952437 Mgi Jnum  J:245082
Mgi Id  MGI:5914837 Doi  10.7554/eLife.31362
Citation  Losa M, et al. (2017) A tissue-specific, Gata6-driven transcriptional program instructs remodeling of the mature arterial tree. Elife 6:e31362
abstractText  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.
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