Journal
JOURNAL OF NEUROSCIENCE
Volume 24, Issue 1, Pages 121-126Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.4071-03.2004
Keywords
dentate; development; granule cell; proliferation; Wnt; LRP6
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Funding
- NIMH NIH HHS [R01 MH066084, MH66084] Funding Source: Medline
- NINDS NIH HHS [K08 NS002208, NS002208] Funding Source: Medline
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LRP6 mutant mice have generalized defects in the Wnt/beta-catenin signaling pathway because of the crucial function of LRP6 as a Wnt signaling co-receptor (Pinson et al., 2000). We examined the hippocampal phenotype of single LRP6 mutant mice as well as LRP6/Lef1 double mutant mice. LRP6 mutants had reduced production of dentate granule neurons and abnormalities of the radial glial scaffolding in the forming dentate gyrus. These defects were more severe with the addition of a single Lef1 null allele to an LRP6 null background. Pyramidal cell fields were unaffected in the LRP6, Lef1, or double mutants. The dentate defects were accompanied by decreased numbers of mitotic precursors in the migratory pathway to the dentate and in the displaced proliferative zone in the dentate itself. At earlier gestational ages, there was a reduction in the number of dentate granule cell progenitors in the dentate ventricular zone before the emigration of the earliest differentiated granule neurons and precursors to form the dentate anlage.
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