Wnt signaling mutants have decreased dentate granule cell production and radial glial scaffolding abnormalities.
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.
Zhou
Cheng-Ji
CJ
Department of Neurology, Programs in Neuroscience and Developmental Biology, University of California, San Francisco, California 94143-0435, USA.
Zhao
Chunjie
C
Pleasure
Samuel J
SJ
D000483:Alleles; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics; D018891:Dentate Gyrus / Q000166:cytology* / Q000196:embryology*; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D051821:Lymphoid Enhancer-Binding Factor 1; D051379:Mice; D018345:Mice, Knockout; D009457:Neuroglia / Q000166:cytology*; D009474:Neurons / Q000166:cytology*; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D011973:Receptors, LDL / Q000235:genetics; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology; D014157:Transcription Factors / Q000235:genetics; D051153:Wnt Proteins; D029961:Zebrafish Proteins
D004268:DNA-Binding Proteins; C497574:Lef1 protein, mouse; D060488:Low Density Lipoprotein Receptor-Related Protein-6; C555476:Lrp6 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D011518:Proto-Oncogene Proteins; D011973:Receptors, LDL; D014157:Transcription Factors; D051153:Wnt Proteins; D029961:Zebrafish Proteins