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

Marta Losa Llabata, Victor Latorre, Munazah Andrabi, Franck Ladam, Charles Sagerström, Ana Nóvoa, Peyman Zarrineh, Laure Bridoux, Neil Hanley, Moises Mallo, Nicoletta Bobola

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
JournaleLife
Early online date27 Sept 2017
DOIs
Publication statusPublished - 27 Sept 2017

Keywords

  • great vessels
  • embryo
  • GATA
  • Transcription
  • smooth muscle cells
  • Neural crest

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