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β-catenin–mediated Wnt signaling regulates neurogenesis in the ventral telencephalon

Nature Neuroscience volume 11, pages 1383–1391 (2008)Cite this article

Abstract

Development of the telencephalon involves the coordinated growth of diversely patterned brain structures. Previous studies have demonstrated the importance of β-catenin–mediated Wnt signaling in proliferation and fate determination during cerebral cortical development. We found that β-catenin–mediated Wnt signaling critically maintained progenitor proliferation in the subcortical (pallidal) telencephalon. Targeted deletion of β-catenin in mice severely impaired proliferation in the medial ganglionic eminence without grossly altering differentiated fate. Several lines of evidence suggest that this phenotype is primarily the result of a loss of canonical Wnt signaling. As previous studies have suggested that the ventral patterning factor Sonic Hedgehog (Shh) also stimulates dorsal telencephalic proliferation, we propose a model whereby Wnt and Shh signaling promote distinct dorsal-ventral patterning while also having broader effects on proliferation that serve to coordinate the growth of telencephalic subregions.

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Figure 1: Loss of β-catenin expression in the ventral pallidum impairs growth of the MGE.
Figure 2: Deletion of β-catenin in MGE progenitors causes decreased proliferation and precocious neuronal differentiation.
Figure 3: Loss of β-catenin expression in MGE progenitors reduces the detection of Nkx2.1-lineage cells at E19.
Figure 4: Canonical Wnt activity is present in the ventral telencephalon.
Figure 5: Canonical Wnt activity is reduced in the MGE of Nkx2.1-cre; Ctnnb1loxP/loxP mutants.
Figure 6: Inhibition of β-catenin–mediated Tcf activation downregulates proliferation in MGE progenitors.
Figure 7: Inhibition of Wnt signaling suppresses proliferation of MGE progenitors.

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Acknowledgements

We thank M.P. Matise for helpful discussions and Q. Xu (Nkx2.1Cre), D. Dufort (Tcf-LacZ), R. Kemler (β-catenin Jackson Laboratory), K. Campbell (Dlx5/6Cre) and E. Morrisey (Wnt7b-lacZ embryos) for providing mice. We thank M.P. Matise (Tcf4 riboprobe), O. Marin (Nkx5.1 riboprobe) and S. Pleasure (drLef1-gfp construct) for probes and reagents. We also thank S. LoCurto for her technical assistance. This work was supported by research grants to S.A.A. from the US National Institutes of Health (P01 NS048120 and K02MH070031).

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  1. Alexandra A Gulacsi

    Present address: Present address: Laboratory of Developmental Neurobiology, Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.,

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  1. Department of Psychiatry, Weill Medical College of Cornell University, 1300 York Avenue, Box 244, New York, 10065, New York, USA

    Alexandra A Gulacsi & Stewart A Anderson

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A.A.G. and S.A.A. designed the experiments; A.A.G. carried out the experiments and analyzed the data; and A.A.G. and S.A.A. wrote the paper.

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Correspondence to Stewart A Anderson.

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Gulacsi, A., Anderson, S. β-catenin–mediated Wnt signaling regulates neurogenesis in the ventral telencephalon. Nat Neurosci 11, 1383–1391 (2008). https://doi.org/10.1038/nn.2226

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