Download Liver X Receptorβ inhibits the transformation of radial glial cells into

Liver X Receptor β inhibits the transformation of radial glial cells into astrocytes
during cerebral cortex development
Liang Guo1，Pei Xu2，Tingting Zhao3, Wenqiong Guo1, Yan Xing2 ，Yuzhang Wu 3, Jan-Ake
Gustafsson4, Haiwei Xu1* , Xiaotang Fan2*
1
Department of Physiology, Third Military Medical University, Chongqing, 400038, PR China
2
Department of Histology and Embryology, Third Military Medical University, Chongqing,
400038, PR China
3
Department of Immunology, Third Military Medical University, Chongqing, 400038, PR China
4
Center for Nuclear Receptors and Cell Signaling, University of Houston, TX 77054
*Corresponding authors：E-mail addresses
Haiwei Xu :[email protected]
Xiaotang Fan:fanxiaotang [email protected] ,
Liver X receptor is a member of the nuclear receptor superfamily of ligand-activated
transcription factors, predominantly expressed in the cerebral cortex. We have previously
demonstrated that LXRβ is essential for migration of later-born neurons during cerebral cortex
development. The radial glial cells serve as scaffolds for new-born neurons migration during
cerebral cortex development. Normally, the radial glial cells were transformationed into astrocytes
around postnatal 14 days. Here, We found that the expression of LXRβ mRNA was higher than
LXRα in the cerebral cortex of mice, of which the expression of LXRβ was gradually increased
from E18.5 to P14. With specific markers for radial glia cells , we further
found that loss of
LXRβ induced the decreased level of BLBP in the cerebral cortex from E18.5 to P7 and increased
level of GFAP from P2 to P14 compared to the WT littermates at the same age. TGF-β1 and
Smad4 are believed to be related to the transformation of radial glial cells into
astrocytes.The expression levels of TGF-β1 and Smad4 were increased significantly in the
cerebral cortex of LXRβ knockout mice compared to the WT littermates from the E18.5 to P7.
There’s no difference in the expression levels of TGF-β1 and Smad4 between the LXRβ knockout
mice and WT littermates from the P10 to P14. Taken together, our findings suggest that loss of
LXRβ accelerate the transformation of radial glial cells into astrocytes through high level of
TGF-β1 and Smad4 in the cerebral cortex.