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Investigating Tonic Wnt Signaling Throughout the Adult CNS and in the Hippocampal Neurogenic Niche of BatGal and Ins-TopGal Mice

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Abstract

Wnt/β-catenin signaling has a well-established role in the development of the central nervous system (CNS), and recent evidence is extending this role to include the regulation of adult hippocampal function, including neurogenesis within the dentate gyrus. While the neuroanatomical expression pattern of many canonical Wnt signaling components have been investigated, the sites of signal integration and functional downstream β-catenin activation remain comparatively less characterized in the adult CNS. Using two independent transgenic β-catenin-activated LacZ reporter mouse lines (BatGal and ins-TopGal), we demonstrate that Wnt/β-catenin signaling is active in discrete regions of the adult mouse CNS. Intriguingly, BatGal mice exhibit a broad pattern of reporter expression in the CNS, while expression in ins-TopGal mice is more restricted. Further investigation of these two lines reveals temporal differences in β-catenin-activated reporter expression during neurogenesis within the adult hippocampus. Ins-TopGal mice display peaks of Wnt/β-catenin-activated reporter expression during early and later stages of neurogenesis suggesting Wnt/β-catenin signaling plays an important role during both progenitor cell amplification as well as neuronal maturation, integration, and/or maintenance; however, results from BatGal mice are not as convincing. Thus our data using ins-TopGal mice are consistent with the idea that Wnt signaling plays diverse roles during adult hippocampal neurogenesis and support the idea that multiple transgenic reporter lines must be rigorously compared during scientific investigations.

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Acknowledgments

We’d like to thank the RIKEN Institute for preparation of the ins-TopGal tissue and the laboratories of Drs. Akira Kudo and Yumiko Saga for use of the ins-TopGal mouse line (Moriyama et al. 2007).

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  1. Pfizer Neuroscience, Pfizer, Worldwide Research and Development, Eastern Point Road, Groton, CT, 06340, USA

    David S. Garbe & Robert H. Ring

  2. Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, 10-165 Translational Research Center, 3400 Civic Center Boulevard Building, 421, Philadelphia, PA, 19104-5158, USA

    David S. Garbe

  3. Translational Research, Autism Speaks, 1060 State Road, Princeton, NJ, 08540, USA

    Robert H. Ring

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Garbe, D.S., Ring, R.H. Investigating Tonic Wnt Signaling Throughout the Adult CNS and in the Hippocampal Neurogenic Niche of BatGal and Ins-TopGal Mice. Cell Mol Neurobiol 32, 1159–1174 (2012). https://doi.org/10.1007/s10571-012-9841-3

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