Open AccessGATA4/5/6 family transcription factors are conserved determinants of cardiac versus pharyngeal mesoderm fate
Author(s) -
Mengyi Song,
Xuefei Yuan,
Claudia Racioppi,
Meaghan Leslie,
Nathan Stutt,
Anastasiia Aleksandrova,
Lionel Christiaen,
Michael D. Wilson,
Ian C. Scott
Publication year - 2022
Publication title -
science advances
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.928
H-Index - 146
ISSN - 2375-2548
DOI - 10.1126/sciadv.abg0834
Subject(s) - mesoderm , gata4 , transcription factor , genetics , fgf and mesoderm formation , biology , gene , embryonic stem cell
GATA4/5/6 transcription factors play essential, conserved roles in heart development. To understand how GATA4/5/6 modulates the mesoderm-to-cardiac fate transition, we labeled, isolated, and performed single-cell gene expression analysis on cells that expressgata5 at precardiac time points spanning zebrafish gastrulation to somitogenesis. We found that most mesendoderm-derived lineages had dynamicgata5/6 expression. In the absence of Gata5/6, the population structure of mesendoderm-derived cells was substantially altered. In addition to the expected absence of cardiac mesoderm, we confirmed a concomitant expansion of cranial-pharyngeal mesoderm. Moreover, Gata5/6 loss led to extensive changes in chromatin accessibility near cardiac and pharyngeal genes. Functional analyses in zebrafish and the tunicateCiona , which has a single GATA4/5/6 homolog, revealed that GATA4/5/6 acts upstream oftbx1 to exert essential and cell-autonomous roles in promoting cardiac and inhibiting pharyngeal mesoderm identity. Overall, cardiac and pharyngeal mesoderm fate choices are achieved through an evolutionarily conserved GATA4/5/6 regulatory network.