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Lef/Tcf-dependent Wnt/b-catenin Signaling Pathway And Xenopus Early Development

Posted on:2004-02-06Degree:DoctorType:Dissertation
Country:ChinaCandidate:X GengFull Text:PDF
GTID:1100360122471007Subject:Developmental Biology
Abstract/Summary:PDF Full Text Request
During Xenopus early development, Wnt/(-catenin signaling pathway functions at various levels, from early embryonic pattern formation to later organgenesis. It is generally believed that upon the stimulation of Wnt signals, stabilized (-catenin regulates target genes' expression via cooperating with Lef/Tcf transcription factors. Recent reports, however, suggest that transcription factors different from Lef/Tcf may mediate Wnt/(-catenin activity. These studies raise the possibility that during Xenopus early development, Wnt/(-catenin signaling pathway may recruit downstream effectors other than Lef/Tcf to achieve cell-specific response to Wnt activity. Thus, what are the endogenous roles that Lef/Tcf-dependent Wnt/(-catenin signaling plays during Xenopus early development? Namely, what is the molecular mechanism underlying these developmental processes? To investigate this issue, we adopts various techniques, such as transgenesis, microinjection, reporter gene assay and explanation, and our results show:1. During Xenopus early development, Lef/Tcf-dependent Wnt/(-catenin activity harbors in the Nieuwkoop center, the Spemann organizer, the ventro-lateral mesoderm and part of mid-brain.Endogenous Lef/Tcf activity is required for the posterior development of2. Xenopus embryo.3. The 6.8 kb of Xmyf-5 5' upstream fragment recapitulates the expression pattern of endogenous Xmyf-5 from early-gastrula stage through tailbud stage. Two Lef/Tcf binding sites within the genomic contig may mediate the organizer-specific activation of Xmyf-5 in early-gastrula. The same sites, however, may also mediate the mid-line-repression at mid-gastrula stage possibly due to the change of active cytoplasmic components.4. The 2.066 kb of Xenopus noggin 5' upstream fragment drives roof-plate-specific transcription and this tissue-specific activation is not mediated by the unique Lef/Tcf binding site within the upstream sequence.5. In Xenopus embryo, neural specification could happen in the absence of dorsal mesoderm. It is quite possible that maternal β-catenin activity plays a key role in this process.In summary, our results indicate that Lef/Tcf-dependent Wnt/(-catenin signaling pathway is involved in dorsal-ventral and anterior-posterior axis specification, as well as the specification and early patterning of nervous system. In other developmental processes, however, Wnt/(-catenin signaling pathway may recruit transcription factors different from Lef/Tcf.
Keywords/Search Tags:Xenopus, Wnt, β-catenin, Tcf/Lef, Xmyf-5, noggin, axis specification, neural development
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