PUBLICATION

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

Authors
Song, M., Yuan, X., Racioppi, C., Leslie, M., Stutt, N., Aleksandrova, A., Christiaen, L., Wilson, M.D., Scott, I.C.
ID
ZDB-PUB-220312-5
Date
2022
Source
Science advances   8: eabg0834 (Journal)
Registered Authors
Aleksandrova, Anastasiia, Leslie, Meaghan, Scott, Ian, Song, Mengyi, Yuan, Xuefei
Keywords
none
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
PubMed
35275720 Full text @ Sci Adv
Abstract
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.
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