Essential Role of the Transcription Factor Ets-2 inXenopus Early Development

Abstract

The fibroblast growth factor (FGF)/MAPK pathway plays an important role in early Xenopus developmental processes, including mesoderm patterning. The activation of the MAPK pathway leads to induction of Xenopus Brachyury (Xbra), which regulates the transcription of downstream mesoderm-specific genes in mesoderm patterning. However, the link between the FGF/MAPK pathway and the induction of Xbra has not been fully understood. Here we present evidence suggesting that Ets-2 is involved in the induction of Xbra and thus in the development of posterior mesoderm during early embryonic development. Overexpression of Ets-2 caused posteriorized embryos and led to the induction of mesoderm in ectodermal explants. Expression of a dominant-negative form of Ets-2 or injection of antisense morpholino oligonucleotides against Ets-2 inhibited the formation of the trunk and tail structures. Overexpression of Ets-2 resulted in the induction of Xbra, and expression of the dominant-negative Ets-2 inhibited FGFor constitutively active MEK-induced Xbra expression. Moreover, overexpression of Ets-2 up-regulated the transcription from Xbra promoter reporter gene constructs. Ets-2 bound to the Xbra promoter region in vitro. These results taken together indicate that Xenopus Ets-2 plays an essential role in mesoderm patterning, lying between the FGF/MAPK pathway and the Xbra transcription.

Integration of Wnt and FGF signaling in the Xenopus gastrula at TCF and Ets binding sites shows the importance of short-range repression by TCF in patterning the marginal zone

“…We took a genome-wide approach and performed ChIP-seq on a triple-FLAG-tagged Ets2. As previously reported, Ets2 acts downstream of FGF signaling as the main effector during Xenopus mesoderm development (Kawachi et al, 2003). Indeed, overexpression (1 ng) of the triple-FLAG-tagged Ets2 results in a posteriorized phenotype very similar to FGF8b overexpression (Fig.…”

“…During gastrulation, multiple FGF ligands, but most notably the FGF8 ligand, are expressed at the posterior end of the embryo (Fletcher et al, 2006;Christen and Slack, 1997) and canonically signal through RAS-MAPK intracellular proteins (Ribisi et al, 2000;Umbhauer et al, 1995;Carballada et al, 2001). Subsequently, downstream of MAPK, Ets2 is phosphorylated and is essential for activating target genes involved in posterior patterning (Kawachi et al, 2003).…”

Analysis of the fibroblastic growth factor receptor-RAS/RAF/MEK/ERK-ETS2/brachyury signalling pathway in chordomas

“…41,42 Furthermore, rearrangements involving ETS2 have been detected in other neoplasms including acute megakaryocytic leukaemia, acute non-lymphoblastic leukaemia and prostatic cancer. 17,43,44 However, the 'in-house' break-apart BAC probe failed to show a rearrangement in this gene in 23 chordomas.…”

How was the notochord born?

“…In Ciona embryos, FGF9/16/20 is involved in the initiation of Ci‐Bra expression, whereas FGF8/17/18 functions together with FGF9/16/20 in the maintenance of Ci‐Bra expression (Yasuo and Hudson ); however, the molecular mechanism of Brachyury expression by FGF remains to be elucidated. In Xenopus and zebrafish embryos, the FGF‐signaling pathway acts upstream of Brachyury expression (Griffin et al ; Schulte‐Merker and Smith ; Kawachi et al ). Two studies have shown that Brachyury and FGF regulate one another's expression (Griffin et al ; Casey et al ).…”