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bioRxiv · 10.1101/2020.01.14.905919

Canonical Wnt-signaling modulates the tempo of dendritic growth of adult-born hippocampal neurons

Heppt, J.·Wittman, M.-T.·Zhang, J.·Vogt-Weisenhorn, D.·Prakash, N.·Wurst, W.·Taketo, M. M. M.·Lie, D. C.
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Abstract

In adult hippocampal neurogenesis neural stem/progenitor cells generate new dentate granule neurons that contribute to hippocampal plasticity. The establishment of a morphologically defined dendritic arbor is central to the functional integration of adult-born neurons. Here, we investigated the role of canonical Wnt/{beta}-catenin-signaling in dendritogenesis of adult-born neurons. We show that canonical Wnt-signaling follows a biphasic pattern, with high activity in stem/progenitor cells, attenuation in early immature neurons, and re-activation during maturation, and demonstrate that the biphasic activity pattern is required for proper dendrite development. Increasing {beta}-catenin-signaling in maturing neurons of young adult mice transiently accelerated dendritic growth, but eventually resulted in dendritic defects and excessive spine numbers. In middle-aged mice, in which protracted dendrite and spine development was paralleled by lower canonical Wnt-signaling activity, enhancement of {beta}-catenin-signaling restored dendritic growth and spine formation to levels observed in young adult animals. Our data indicate that precise timing and strength of {beta}-catenin-signaling is essential for the correct functional integration of adult-born neurons and suggest Wnt/{beta}-catenin-signaling as a pathway to ameliorate deficits in adult neurogenesis during aging.

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Heppt, J., Wittman, M.-T., Zhang, J., Vogt-Weisenhorn, D., Prakash, N., Wurst, W., Taketo, M. M. M., Lie, D. C.. 2020-01-15. Canonical Wnt-signaling modulates the tempo of dendritic growth of adult-born hippocampal neurons. https://doi.org/10.1101/2020.01.14.905919

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