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β-catenin is critical for dendritic morphogenesis

Nature Neuroscience volume 6, pages 1169–1177 (2003)Cite this article

Abstract

Regulated growth and arborization of dendritic processes are critical to the formation of functional neuronal networks. Here we identify β-catenin as a critical mediator of dendritic morphogenesis. We found that increasing the intracellular levels of β-catenin and other members of the cadherin/catenin complex, namely N-cadherin and αN-catenin, enhances dendritic arborization in rat hippocampal neurons, an effect that does not require Wnt/β-catenin-dependent transcription. Conversely, proteins that sequester β-catenin decreased dendritic branch tip number and total dendritic branch length. Enhancement of dendritic growth elicited by depolarization requires β-catenin and increased Wnt release. These results identify Wnt/β-catenin signaling as an important mediator of dendritic development and suggest that the intracellular level of the cadherin/catenin complex is a limiting factor during critical stages of dendritic morphogenesis.

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Figure 1: β-catenin* expression causes an increase in TDBTN.
Figure 2: Correlation between β-catenin levels and TDBTN.
Figure 3: Ncad(intra) reduces TDBTN by sequestering endogenous β-catenin.
Figure 4: Expression of other members of the cadherin/catenin complex increases TDBTN.
Figure 5: The effects of β-catenin on dendritic branching do not require nuclear signaling.
Figure 6: The effects of neural activity on dendritic morphogenesis.
Figure 7: A central role for β-catenin in activity-dependent dendritic morphogenesis.
Figure 8: A critical role for Wnt signaling in activity-dependent regulation of dendritic arborization.

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Acknowledgements

We thank A. Barth, W. J. Nelson, S. Bamji, L. Reichardt, D. Benson, D. Colman, S. Aaronson, T. Chatila, H. Clevers, R. Grosschedl, L. Luo, P. McCrea, M. Waterman, and L. Ailles for DNA constructs, K. Deisseroth and S. Singla for the Wnt conditioned medium, and N. Calakos for the astryocyte cultures. We thank T. Lizama, L. Esaura and J. Fisher for hippocampal culture preparation and excellent technical assistance. We are grateful to C. Garner, L. Luo, K. Deisseroth and S. Singla for comments on the manuscript and to members of the Malenka lab for discussion. This work was supported by grants from the National Institutes of Health (to R.C.M) and a Wellcome International Prize Travelling Research Fellowship (to X.Y.).

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  1. Department of Psychiatry and Behavioral Sciences, Nancy Friend Pritzker Laboratory, Stanford University School of Medicine, Palo Alto, 94304, California, USA

    Xiang Yu & Robert C Malenka

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Correspondence to Xiang Yu or Robert C Malenka.

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Yu, X., Malenka, R. β-catenin is critical for dendritic morphogenesis. Nat Neurosci 6, 1169–1177 (2003). https://doi.org/10.1038/nn1132

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