Neuronal production and precursor proliferation defects in the neocortex of mice with loss of function in the canonical Wnt signaling pathway

Chengji Zhou, U. Borello, J. L R Rubenstein, S. J. Pleasure

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

To better understand the function of the Wnt pathway in the developing telencephalon, we analyzed neocortical development in low density lipoprotein receptor-related protein (LRP) 6 mutants. LRP6 mutant mice are hypomorphic for the canonical Wnt signaling pathway and have hypoplasia of the developing neocortex. While early telencephalic morphogenesis is largely intact in these mice, probably due to compensation by LRP5, the mutant mice develop a dramatically thinner cortical plate. There is a prominent reduction of neurogenesis leading to a thin cortical plate. Reduced proliferation late in gestation probably also contributes to the hypoplasia. Although there are marked decreases in the numbers of layer 6 and layers 2-4 neurons all laminar identities are generated and there is no evidence of compensatory increases in layer 5 neurons. In addition, LRP6 mutants have partial penetrance of a complex of cortical dysmorphologies resembling those found in patients with developmental forms of epilepsy and mental retardation. These include ventricular and marginal zone heterotopias and cobblestone lissencephaly. This analysis demonstrates that canonical Wnt signaling is required for a diverse array of developmental processes in the neocortex in addition to the previously known roles in regulating precursor proliferation and patterning.

Original languageEnglish (US)
Pages (from-to)1119-1131
Number of pages13
JournalNeuroscience
Volume142
Issue number4
DOIs
StatePublished - Nov 3 2006

Fingerprint

Wnt Signaling Pathway
Neocortex
Telencephalon
Cerebral Cortex
Cobblestone Lissencephaly
Low Density Lipoprotein Receptor-Related Protein-6
Neurons
Penetrance
Neurogenesis
Morphogenesis
Intellectual Disability
Epilepsy
Pregnancy

Keywords

  • cortical lamination
  • heterotopia
  • lissencephaly
  • neocortex
  • neural precursor
  • neurogenesis

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Neuronal production and precursor proliferation defects in the neocortex of mice with loss of function in the canonical Wnt signaling pathway. / Zhou, Chengji; Borello, U.; Rubenstein, J. L R; Pleasure, S. J.

In: Neuroscience, Vol. 142, No. 4, 03.11.2006, p. 1119-1131.

Research output: Contribution to journalArticle

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