Mesodermal Wnt signaling organizes the neural plate via Meis3.
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.
Elkouby
Yaniv M
YM
Department of Biochemistry, The Rappaport Family Institute for Research in the Medical Sciences, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel.
Elias
Sarah
S
Casey
Elena S
ES
Blythe
Shelby A
SA
Tsabar
Nir
N
Klein
Peter S
PS
Root
Heather
H
Liu
Karen J
KJ
Frank
Dale
D
D000818:Animals; D047369:Chromatin Immunoprecipitation; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D008648:Mesoderm / Q000196:embryology*; D054258:Neural Plate / Q000196:embryology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
D018398:Homeodomain Proteins; C491174:Meis3 protein, Xenopus; C555506:WNT3A protein, Xenopus; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin