In adult hippocampal neurogenesis, stem/progenitor cells generate 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. We investigated the role of canonical Wnt/β‐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 immature neurons, and reactivation during maturation, and demonstrate that this activity pattern is required for proper dendrite development. Increasing β‐catenin signaling in maturing neurons of young adult mice transiently accelerated dendritic growth, but eventually produced dendritic defects and excessive spine numbers. In middle‐aged mice, in which protracted dendrite and spine development were paralleled by lower canonical Wnt signaling activity, enhancement of β‐catenin signaling restored dendritic growth and spine formation to levels observed in young adult animals. Our data indicate that precise timing and strength of β‐catenin signaling are essential for the correct functional integration of adult‐born neurons and suggest Wnt/β‐catenin signaling as a pathway to ameliorate deficits in adult neurogenesis during aging.
SOX11 is a key Transcription Factor (TF) in the regulation of embryonic and adult neurogenesis, whose mutation has recently been linked to an intellectual disability syndrome in humans. SOX11’s transient activity during neurogenesis is critical to ensure the precise execution of the neurogenic program. Here, we report that SOX11 displays differential subcellular localizations during the course of neurogenesis. Western-Blot analysis of embryonic mouse brain lysates indicated that SOX11 is post-translationally modified by phosphorylation. Using Mass Spectrometry, we found 10 serine residues in the SOX11 protein that are putatively phosphorylated. Systematic analysis of phospho-mutant SOX11 resulted in the identification of the S30 residue, whose phosphorylation promotes nuclear over cytoplasmic localization of SOX11. Collectively, these findings uncover phosphorylation as a novel layer of regulation of the intellectual disability gene Sox11.
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/-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 -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 catenin-signaling restored dendritic growth and spine formation to levels observed in young adult animals. Our data indicate that precise timing and strength of -catenin-signaling is essential for the correct functional integration of adult-born neurons and suggest Wnt/catenin-signaling as a pathway to ameliorate deficits in adult neurogenesis during aging.
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