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Effect of canonical Wnt inhibition in the neurogenic cortex, hippocampus, and premigratory dentate gyrus progenitor pool.
Authors:Nina Solberg  Ondrej Machon  Stefan Krauss
Institution:Section for Cellular and Genetic Therapy, Institute of Microbiology, Rikshospitalet, Oslo, Norway. Nina.Therese.Solberg@rr-research.no
Abstract:Canonical Wnt signaling is crucial for the correct development of both cortical and hippocampal structures in the dorsal telencephalon. In this study, we examined the role of the canonical Wnt signaling in the dorsal telencephalon of mouse embryos at defined time periods by inhibition of the pathway with ectopic expression of Dkk1. Transgenic mice with the D6-driven Dkk1 gene exhibited reduced canonical Wnt signaling in the cortex and hippocampus. As a result, all hippocampal fields were reduced in size. Neurogenesis in the dentate gyrus was severely reduced both in the premigratory and migratory progenitor pool. The lower number of progenitors in the dentate gyrus was not rescued after migration to the subgranular zone and thus the dentate gyrus lacked the entire internal blade and a part of the external blade from postnatal to adult stages.
Keywords:hippocampus  dentate gyrus  Wnt signaling  Dickkopf1  neurogenesis  proliferation
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