GATA transcription factors integrate Wnt signalling during heart development.
Cardiogenesis is inhibited by canonical Wnt/beta-catenin signalling and stimulated by non-canonical Wnt11/JNK signalling, but how these two signalling pathways crosstalk is currently unknown. Here, we show that Wnt/beta-catenin signalling restricts cardiogenesis via inhibition of GATA gene expression, as experimentally reinstating GATA function overrides beta-catenin-mediated inhibition and restores cardiogenesis. Furthermore, we show that GATA transcription factors in turn directly regulate Wnt11 gene expression, and that Wnt11 is required to a significant degree for mediating the cardiogenesis-promoting function of GATA transcription factors. These results demonstrate that GATA factors occupy a central position between canonical and non-canonical Wnt signalling in regulating heart muscle formation.
Afouda
Boni A
BA
Institute of Medical Sciences, Cell and Developmental Biology Research Programme, School of Medical Sciences, University of Aberdeen, Aberdeen, UK.
Martin
Jennifer
J
Liu
Fei
F
Ciau-Uitz
Aldo
A
Patient
Roger
R
Hoppler
Stefan
S
D000818:Animals; D050980:GATA Transcription Factors / Q000235:genetics / Q000378:metabolism*; D050991:GATA4 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D050993:GATA6 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D014981:Xenopus / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029867:Xenopus Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
C495266:CTNNB1 protein, Xenopus; D050980:GATA Transcription Factors; D050991:GATA4 Transcription Factor; C494751:GATA4 protein, Xenopus; D050993:GATA6 Transcription Factor; C494758:GATA6 protein, Xenopus; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C092720:NKX2-5 protein, Xenopus; D012333:RNA, Messenger; D014157:Transcription Factors; D051153:Wnt Proteins; D029867:Xenopus Proteins; D051176:beta Catenin; C512785:wnt11b protein, Xenopus