Effect of canonical Wnt inhibition in the neurogenic cortex, hippocampus, and premigratory dentate gyrus progenitor pool

Dev Dyn. 2008 Jul;237(7):1799-811. doi: 10.1002/dvdy.21586.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Cerebral Cortex / cytology
  • Cerebral Cortex / embryology
  • Cerebral Cortex / metabolism*
  • Dentate Gyrus / cytology
  • Dentate Gyrus / embryology
  • Dentate Gyrus / metabolism*
  • Gene Expression Regulation, Developmental
  • Hippocampus / cytology
  • Hippocampus / embryology
  • Hippocampus / metabolism*
  • Immunohistochemistry
  • In Situ Hybridization
  • In Situ Nick-End Labeling
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Intercellular Signaling Peptides and Proteins / physiology
  • Mice
  • Mice, Transgenic
  • Promoter Regions, Genetic / genetics
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism*
  • Wnt Proteins / physiology

Substances

  • Dkk1 protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Wnt Proteins