Wnt signalling required for expansion of neural crest and CNS progenitors

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Abstract

Interactions between cells help to elaborate pattern within the vertebrate central nervous system (CNS)1. The genes Wnt-1 and Wnt-3a, which encode members of the Wnt family of cysteine-rich secreted signals, are coexpressed at the dorsal midline of the developing neural tube, coincident with dorsal patterning2,3. Each signal is essential for embryonic development, Wnt-1 for midbrain patterning4,5 and Wnt-3a for formation of the paraxial mesoderm6, but the absence of a dorsal neural-tube phenotype in each mutant suggests that Wnt signalling may be redundant. Here we demonstrate that in the absence of both Wnt-1 and Wnt-3a there is a marked deficiency in neural crest derivatives, which originate from the dorsal neural tube7, and a pronounced reduction in dorsolateral neural precursors within the neural tube itself. These phenotypes do not seem to result from a disruption in the mechanisms responsible for establishing normal dorsoventral polarity. Rather, our results are consistent with a model in which local Wnt signalling regulates the expansion of dorsal neural precursors. Given the widespread expression of different Wnt genes in discrete areas of the mammalian neural tube3, this may represent a general model for the action of Wnt signalling in the developing CNS.

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Figure 1: Analysis of neuronal patterning in Wnt-1/Wnt-3a compound mutants.
Figure 2: Analysis of the expression of neuronal and glial markers in Wnt-1/Wnt-3a compound mutants.
Figure 3: Analysis of the expression of neural crest cell markers in Wnt-1/Wnt-3a compound mutants.
Figure 4: Cranial skeleton of Wnt-1/Wnt-3a compound mutant embryos at 18.
Figure 5: Analysis of dorsal–ventral polarity in the hindbrain of Wnt-1/Wnt-3a compound mutants.

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Acknowledgements

We thank M. Takeichi for discussion and the cadherin-6 complementary DNA probe; U. Eriksson and N. Ohsumi for the CRABP-1 polyclonal antibody; T. Jessell for the Islet-1 cDNA probe; A. Dudley for the Bmp-7 cDNA probe; T. Williams for the AP-2 cDNA probe; M. Takahashi for the c-ret cDNA probe; P. Gruss for Pax-3 and Pax-6 cDNA probes; and I. Jackson for the TRP-2 cDNA probe. This work was supported by a grant-in-aid for Creative Fundamental Research from the Ministry of Education, Science, and Culture of Japan (S.T.), a grant from the Kent Waldrep National Paralysis Foundation (J.E.J.) and a grant from the NIH (A.P.M.).

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Correspondence to Andrew P. McMahon or Shinji Takada.

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