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.
RNA-seq analysis of branchial arches and outflow tract of the mouse embryo at E10.5 and E11.5Publicly available at EBI.
ChIP-seq for Meis on mouse branchial arches at E11.5Publicly available at EBI.
ChIP-seq for Gata6 and histone H3K27Ac on mouse branchial arches at E11.5Publicly available at EBI.
Reinstatement of developmental stage-specific GATA4 enhancers controls the gene expression program in heart diseaseGata4 ChIP-seqPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE52123).
Gene bivalency at Polycomb domains regulates cranial neural crest positional identity [ATAC-seq]ATAC-seq BA2Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE89436).
- Nicoletta Bobola
- Nicoletta Bobola
- Charles Sagerström
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: Experiments on animals followed the local (ASPA 1986, UK; Portaria 1005/92 and Directive 2010/63/EU, P) legislations concerning housing, husbandry, and welfare.
- Marianne Bronner, California Institute of Technology, United States
© 2017, Losa et al.
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