GATA4/5/6 family transcription factors are conserved determinants of cardiac versus pharyngeal mesoderm fate

Sci Adv. 2022 Mar 11;8(10):eabg0834. doi: 10.1126/sciadv.abg0834. Epub 2022 Mar 11.


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 express gata5 at precardiac time points spanning zebrafish gastrulation to somitogenesis. We found that most mesendoderm-derived lineages had dynamic gata5/6 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 tunicate Ciona, which has a single GATA4/5/6 homolog, revealed that GATA4/5/6 acts upstream of tbx1 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.

MeSH terms

  • Animals
  • GATA4 Transcription Factor* / genetics
  • GATA4 Transcription Factor* / metabolism
  • GATA5 Transcription Factor / genetics
  • GATA5 Transcription Factor / metabolism
  • Gene Expression Regulation, Developmental
  • Mesoderm / metabolism
  • Zebrafish* / genetics
  • Zebrafish* / metabolism


  • GATA4 Transcription Factor
  • GATA5 Transcription Factor