Downstream of FGF during mesoderm formation in Xenopus: the roles of Elk-1 and Egr-1.
Signalling by members of the FGF family is required for induction and maintenance of the mesoderm during amphibian development. One of the downstream effectors of FGF is the SRF-interacting Ets family member Elk-1, which, after phosphorylation by MAP kinase, activates the expression of immediate-early genes. Here, we show that Xenopus Elk-1 is phosphorylated in response to FGF signalling in a dynamic pattern throughout the embryo. Loss of XElk-1 function causes reduced expression of Xbra at neurula stages, followed by a failure to form notochord and muscle and then the partial loss of trunk structures. One of the genes regulated by XElk-1 is XEgr-1, which encodes a zinc finger transcription factor: we show that phosphorylated XElk-1 forms a complex with XSRF that binds to the XEgr-1 promoter. Superficially, Xenopus tropicalis embryos with reduced levels of XEgr-1 resemble those lacking XElk-1, but to our surprise, levels of Xbra are elevated at late gastrula stages in such embryos, and over-expression of XEgr-1 causes the down-regulation of Xbra both in whole embryos and in animal pole regions treated with activin or FGF. In contrast, the myogenic regulatory factor XMyoD is activated by XEgr-1 in a direct manner. We discuss these counterintuitive results in terms of the genetic regulatory network to which XEgr-1 contributes.
Wellcome Trust/Cancer Research UK Gurdon Institute and Department of Zoology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
Oliver
O
Nentwich
Kevin S
KS
Dingwell
A
A
Nordheim
J C
JC
Smith
D000818:Animals; D001483:Base Sequence; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers; D004277:DNA, Single-Stranded / Q000502:physiology*; D005346:Fibroblast Growth Factors / Q000502:physiology*; D017403:In Situ Hybridization; D008648:Mesoderm / Q000196:embryology*; D016133:Polymerase Chain Reaction; D014982:Xenopus laevis / Q000196:embryology*; D050807:ets-Domain Protein Elk-1 / Q000502:physiology*
D017931:DNA Primers; C400152:DNA enzyme ED5; D004277:DNA, Single-Stranded; D050807:ets-Domain Protein Elk-1; D005346:Fibroblast Growth Factors