ZFIN ID: ZDB-PUB-100330-39
Overlapping functions of Pea3 ETS transcription factors in FGF signaling during zebrafish development
Znosko, W.A., Yu, S., Thomas, K., Molina, G.A., Li, C., Tsang, W., Dawid, I.B., Moon, A.M., and Tsang, M.
Date: 2010
Source: Developmental Biology   342(1): 11-25 (Journal)
Registered Authors: Dawid, Igor B., Molina, Gabriela, Tsang, Michael, Znosko, Wade
Keywords: FGF, Pea3 ETS factors, heart, left/right patterning, zebrafish, Kupffer's vesicle, cilia, Dusp6
MeSH Terms:
  • Animals
  • Binding Sites/genetics
  • Cell Differentiation/genetics
  • Fibroblast Growth Factors/genetics
  • Fibroblast Growth Factors/metabolism*
  • Gene Expression
  • Gene Expression Regulation
  • Mice
  • Mitogen-Activated Protein Kinases/genetics
  • Mitogen-Activated Protein Kinases/metabolism
  • Oncogenes
  • Proto-Oncogene Proteins c-ets/genetics
  • Proto-Oncogene Proteins c-ets/metabolism*
  • Signal Transduction/genetics
  • Signal Transduction/physiology
  • Transcription Factors/genetics
  • Transcription Factors/metabolism*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
PubMed: 20346941 Full text @ Dev. Biol.
Fibroblast Growth Factors (FGFs) are secreted molecules that activate the RAS/mitogen-activated protein kinase (MAPK) signaling pathway. In zebrafish development, FGF signaling is responsible for establishing dorsal polarity, maintaining the isthmic organizer, and cardiac ventricle formation. Because several ETS factors are known transcriptional mediators of MAPK signaling, we hypothesized that these factors function to mediate FGF signaling processes. In zebrafish, the simultaneous knock-down of three Pea3 ETS proteins, Etv5, Erm, and Pea3, produced phenotypes reminiscent of embryos deficient in FGF signaling. Morphant embryos displayed both cardiac and left/right patterning defects as well as disruption of the isthmic organizer. Furthermore, the expression of FGF target genes was abolished in Pea3 ETS depleted embryos. To understand how FGF signaling and ETS factors control gene expression, transcriptional regulation of dusp6 was studied in mouse and zebrafish. Conserved Pea3 ETS binding sites were identified within the Dusp6 promoter, and reporter assays showed that one of these sites is required for dusp6 induction by FGFs. We further demonstrated the interaction of Pea3 ETS factors with the Dusp6 promoter both in vitro and in vivo. These results revealed the requirement of ETS factors in transducing FGF signals in developmental processes.