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Development. May 1, 2010; 137 (9): 1531-41.

Mesodermal Wnt signaling organizes the neural plate via Meis3.

Elkouby YM , Elias S , Casey ES , Blythe SA , Tsabar N , Klein PS , Root H , Liu KJ , Frank D .

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/beta-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.

PubMed ID: 20356957
PMC ID: PMC3188567
Article link: Development.
Grant support: R01 GM076621-02 NIGMS NIH HHS , R01 GM076621-03 NIGMS NIH HHS , BB/E013872/1 Biotechnology and Biological Sciences Research Council , R01 GM076621 NIGMS NIH HHS , BB_BB/E013872/1 Biotechnology and Biological Sciences Research Council

Genes referenced: acss2.2 ag1 dkk1 egr2 foxd3 gal.2 gbx2.1 gbx2.2 hesx1 hoxb3 hoxd1 meis3 myl2 odc1 otx2 tub tubb2b wnt3a

Morpholinos referenced: wnt3a MO1 wnt3a MO2 wnt3a MO3

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Aamar, 2003, Pubmed, Xenbase[+]

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