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BMC Dev Biol August 7, 2008; 8 77.

Cold-inducible RNA binding protein (CIRP), a novel XTcf-3 specific target gene regulates neural development in Xenopus.

van Venrooy S , Fichtner D , Kunz M , Wedlich D , Gradl D .

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. CONCLUSION: 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.

PubMed ID: 18687117
PMC ID: PMC2527318
Article link: BMC Dev Biol

Genes referenced: ag1 cirbp eya1 h4c12 hmgb2 hmgn1 hmgn2 lef1 meis3 myc ncam1 odc1 sox2 tcf7 tcf7l1 tcf7l2 tle4 tmem126a
Morpholinos: cirbp MO2 lef1 MO3 lef1 MO4 tcf7l1 MO3 tcf7l2 MO1

Article Images: [+] show captions
References [+] :
Aoki, Methylation of Xenopus CIRP2 regulates its arginine- and glycine-rich region-mediated nucleocytoplasmic distribution. 2002, Pubmed, Xenbase

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