Cold-inducible RNA binding protein (CIRP), a novel XTcf-3 specific target gene regulates neural development in Xenopus.
BACKGROUND
As nuclear mediators of wnt/beta-catenin signaling, Lef/Tcf transcription factors play important roles in development and disease. Although it is well established, that the four vertebrate Lef/Tcfs have unique functional properties, most studies unite Lef-1, Tcf-1, Tcf-3 and Tcf-4 and reduce their function to uniformly transduce wnt/beta-catenin signaling for activating wnt target genes. In order to discriminate target genes regulated by XTcf-3 from those regulated by XTcf-4 or Lef/Tcfs in general, we performed a subtractive screen, using neuralized Xenopus animal cap explants.


RESULTS
We identified cold-inducible RNA binding protein (CIRP) as novel XTcf-3 specific target gene. Furthermore, we show that knockdown of XTcf-3 by injection of an antisense morpholino oligonucleotide results in a general broadening of the anterior neural tissue. Depletion of XCIRP by antisense morpholino oligonucleotide injection leads to a reduced stability of mRNA and an enlargement of the anterior neural plate similar to the depletion of XTcf-3.


CONCLUSIONS
Distinct steps in neural development are differentially regulated by individual Lef/Tcfs. For proper development of the anterior brain XTcf-3 and the Tcf-subtype specific target XCIRP appear indispensable. Thus, regulation of anterior neural development, at least in part, depends on mRNA stabilization by the novel XTcf-3 target gene XCIRP.
van Venrooy
Stephanie
S
Zoologisches Institut II, Universität Karlsruhe (TH), 76131 Karlsruhe, Germany. stephanie.vanvenrooy@zi2.uka.de
Fichtner
Dagmar
D
Kunz
Martin
M
Wedlich
Doris
D
Gradl
Dietmar
D
D000818:Animals; D016375:Antisense Elements (Genetics) / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000196:embryology; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D054258:Neural Plate / Q000196:embryology*; D010641:Phenotype; D020871:RNA Stability / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051820:TCF Transcription Factors / Q000235:genetics*; D058127:Transcription Factor 3; D058125:Transcription Factor 7-Like 1 Protein; D058118:Transcription Factor 7-Like 2 Protein; D014981:Xenopus / Q000196:embryology* / Q000235:genetics; D029867:Xenopus Proteins / Q000235:genetics*
D016375:Antisense Elements (Genetics); C112949:CIRBP protein, Xenopus; C116548:Lef1 protein, Xenopus; D051821:Lymphoid Enhancer-Binding Factor 1; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D051820:TCF Transcription Factors; C544917:Tcf3 protein, Xenopus; D058127:Transcription Factor 3; D058125:Transcription Factor 7-Like 1 Protein; D058118:Transcription Factor 7-Like 2 Protein; D029867:Xenopus Proteins; C544896:tcf7l2 protein, Xenopus