Liver X receptor beta and thyroid hormone receptor alpha in brain cortical layering.
In the past year, two members of the nuclear receptor family, liver X receptor beta (LXRbeta) and thyroid hormone receptor alpha (TRalpha), have been found to be essential for correct migration of neurons in the developing cortex in mouse embryos. TRalpha and LXRbeta bind to identical response elements on DNA and sometimes regulate the same genes. The reason for the migration defect in the LXRbeta(-/-) mouse and the possibility that TRalpha may be involved are the subjects of the present study. At E15.5, expression of reelin and VLDLR was similar but expression of apolipoprotein E receptor 2 (ApoER2) (the reelin receptor) was much lower in LXRbeta(-/-) than in WT mice. Knockout of ApoER2 is known to lead to abnormal cortical lamination. Surprisingly, by postnatal day 14 (P14), no morphological abnormalities were detectable in the cortex of LXRbeta(-/-) mice and ApoER2 expression was much stronger than in WT controls. Thus, a postnatal mechanism leads to increase in ApoER2 expression by P14. TRalpha also regulates ApoER2. In both WT and LXRbeta(-/-) mice, expression of TRalpha was high at postnatal day 2. By P14 it was reduced to low levels in WT mice but was still abundantly expressed in the cortex of LXRbeta(-/-) mice. Based on the present data we hypothesize that reduction in the level of ApoER2 is the reason for the retarded migration of later-born neurons in LXRbeta(-/-) mice but that as thyroid hormone (TH) increases after birth the neurons do find their correct place in the cortex.
Tan
Xin-Jie
XJ
Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, TX 77204, USA.
Fan
Xiao-Tang
XT
Kim
Hyun-Jin
HJ
Butler
Ryan
R
Webb
Paul
P
Warner
Margaret
M
Gustafsson
Jan-Ake
JA
D000818:Animals; D000831:Animals, Newborn; D001923:Brain Chemistry; D002465:Cell Movement; D002540:Cerebral Cortex / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D007150:Immunohistochemistry; D026502:LDL-Receptor Related Proteins; D000071518:Liver X Receptors; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism*; D018110:Receptors, Lipoprotein / Q000378:metabolism; D000091042:Reelin Protein; D037021:Thyroid Hormone Receptors alpha / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
D026502:LDL-Receptor Related Proteins; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018110:Receptors, Lipoprotein; D000091042:Reelin Protein; D037021:Thyroid Hormone Receptors alpha; C098773:low density lipoprotein receptor-related protein 8; C000717128:Reln protein, mouse