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Publication : Role of Cdx factors in early mesodermal fate decisions.

First Author  Foley TE Year  2019
Journal  Development Volume  146
Issue  7 PubMed ID  30936115
Mgi Jnum  J:275052 Mgi Id  MGI:6306607
Doi  10.1242/dev.170498 Citation  Foley TE, et al. (2019) Role of Cdx factors in early mesodermal fate decisions. Development 146(7):dev170498
abstractText  Murine cardiac and hematopoietic progenitors are derived from Mesp1(+) mesoderm. Cdx function impacts both yolk sac hematopoiesis and cardiogenesis in zebrafish, suggesting that Cdx family members regulate early mesoderm cell fate decisions. We found that Cdx2 occupies a number of transcription factor loci during embryogenesis, including key regulators of both cardiac and blood development, and that Cdx function is required for normal expression of the cardiogenic transcription factors Nkx2-5 and Tbx5 Furthermore, Cdx and Brg1, an ATPase subunit of the SWI/SNF chromatin remodeling complex, co-occupy a number of loci, suggesting that Cdx family members regulate target gene expression through alterations in chromatin architecture. Consistent with this, we demonstrate loss of Brg1 occupancy and altered chromatin structure at several cardiogenic genes in Cdx-null mutants. Finally, we provide evidence for an onset of Cdx2 expression at E6.5 coinciding with egression of cardiac progenitors from the primitive streak. Together, these findings suggest that Cdx functions in multi-potential mesoderm to direct early cell fate decisions through transcriptional regulation of several novel target genes, and provide further insight into a potential epigenetic mechanism by which Cdx influences target gene expression.
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