Expression of liver X receptor beta is essential for formation of superficial cortical layers and migration of later-born neurons.
Liver X receptor (LXR) beta 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 LXRbeta protein in the cerebral cortex and looked for defects in cortical development in LXRbeta knockout (LXRbeta(-/-)) mice. LXRbeta 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, LXRbeta was localized mainly in the upper layers of the cerebral cortex. In LXRbeta(-/-) 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 LXRbeta(-/-) 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 LXRbeta(-/-) 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 LXRbeta expression in the cerebral cortex is involved in cortex lamination and is essential for the migration of late-generated neocortical neurons.
Fan
Xiaotang
X
Division of Medical Nutrition, Department of Biosciences and Nutrition, Karolinska Institutet, Novum, S-141 86 Stockholm, Sweden.
Kim
Hyun-Jin
HJ
Bouton
Didier
D
Warner
Margaret
M
Gustafsson
Jan-Ake
JA