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Cited by 103Neurogenesis and neuroplasticity mechanismsFetal and Pediatric Neurological DisordersDevelopmental Biology and Gene Regulation

Expression of liver X receptor β is essential for formation of superficial cortical layers and migration of later-born neurons

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Fan, Xiaotang, Kim, Hyun-Jin, Bouton, Didier, Warner, Margaret, Gustafsson, Jan-Åke·2008·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0806974105PMC PMC2533209
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Abstract

Liver X receptor (LXR) β regulates cholesterol levels in the brain and is essential for maintenance of motor neurons in the spinal cord and dopaminergic neurons in the substantia nigra. Here, we have examined the expression pattern of LXRβ protein in the cerebral cortex and looked for defects in cortical development in LXRβ knockout (LXRβ −/− ) mice. LXRβ protein was widely expressed in the mouse brain at later embryonic stages, and the expression pattern in the cerebral cortex was developmentally regulated. In normal postnatal mice, LXRβ was localized mainly in the upper layers of the cerebral cortex. In LXRβ −/− mice layers II and III were thinner with fewer neurons. Layer I was slightly thicker, whereas layers IV–VI were essentially normal. Consistent with this finding, Brn2 and NeuN expression were decreased in the upper layers in the LXRβ −/− neonatal cortex. The number of S-phase progenitor cells in the cortex between embryonic day (E) 12.5 to E16.5, was similar in WT and LXRβ −/− littermates but BrdU birth dating revealed that late-generated neurons labeled by BrdU injections administered at E14.5 or E16.5, and destined to cortical layers II/III, were disorganized and failed to migrate. The defect in migration appears to be caused by a reduction in the number of vertical processes emanating from the radial glia. These processes are the architectural guides for later-born migrating neurons. Taken together, these findings suggest that LXRβ expression in the cerebral cortex is involved in cortex lamination and is essential for the migration of late-generated neocortical neurons.

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Cited by

Sorted by citations

Authors
Fan, X., Kim, H.-J., Bouton, D., Warner, M., & Gustafsson, J.-Å.
Affiliations
  • Army Medical University (CN)
  • Karolinska Institutet (SE)
  • Houston Methodist (US)
  • *Division of Medical Nutrition, Department of Biosciences and Nutrition, Karolinska Institutet, Novum, S-141 86 Stockholm, Sweden; and
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2008-09-09
Volume
105
Issue
36
Pages
13445-13450
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0806974105
PMC
PMC2533209
OpenAlex
W1967983317
Cited by
103
References
2
Citations by year
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FWCI
1.80
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
liver X receptor beta, cortical development, cortical lamination, neuronal migration, radial glia, Brn2, NeuN, cholesterol metabolism, developmental gene regulation
MeSH terms
Liver X Receptors, Animals, Animals, Newborn, Brain, Cell Movement, DNA-Binding Proteins, Mutation, Neurons, Receptors, Cytoplasmic and Nuclear, Mice, Knockout, Gene Expression Regulation, Developmental, Mice, Orphan Nuclear Receptors

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