Mesodermal Wnt signaling organizes the neural plate via Meis3

Yaniv M. Elkouby, Sarah Elias, Elena S. Casey, Shelby A. Blythe, Nir Tsabar, Peter S. Klein, Heather Root, Karen J. Liu, Dale Frank

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

In vertebrates, canonical Wnt signaling controls posterior neural cell lineage specification. Although Wnt signaling to the neural plate is sufficient for posterior identity, the source and timing of this activity remain uncertain. Furthermore, crucial molecular targets of this activity have not been defined. Here, we identify the endogenous Wnt activity and its role in controlling an essential downstream transcription factor, Meis3. Wnt3a is expressed in a specialized mesodermal domain, the paraxial dorsolateral mesoderm, which signals to overlying neuroectoderm. Loss of zygotic Wnt3a in this region does not alter mesoderm cell fates, but blocks Meis3 expression in the neuroectoderm, triggering the loss of posterior neural fates. Ectopic Meis3 protein expression is sufficient to rescue this phenotype. Moreover, Wnt3a induction of the posterior nervous system requires functional Meis3 in the neural plate. Using ChIP and promoter analysis, we show that Meis3 is a direct target of Wnt/β-catenin signaling. This suggests a new model for neural anteroposterior patterning, in which Wnt3a from the paraxial mesoderm induces posterior cell fates via direct activation of a crucial transcription factor in the overlying neural plate.

Original languageEnglish
Pages (from-to)1531-1541
Number of pages11
JournalDevelopment (Cambridge)
Volume137
Issue number9
DOIs
StatePublished - 1 May 2010
Externally publishedYes

Funding

FundersFunder number
National Institute of General Medical SciencesR01GM076621
Biotechnology and Biological Sciences Research CouncilBB/E013872/1

    Keywords

    • Dorsal-lateral marginal zone (DLMZ)
    • Meis3
    • Neural patterning
    • Paraxial mesoderm
    • Wnt3a
    • Xenopus

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