Format

Send to

Choose Destination
Nucleic Acids Res. 2013 Sep;41(16):7753-70. doi: 10.1093/nar/gkt567. Epub 2013 Jun 26.

LHX2 regulates the neural differentiation of human embryonic stem cells via transcriptional modulation of PAX6 and CER1.

Author information

1
Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei 100, Taiwan, Genomics Research Center, Academia Sinica, Taipei 115, Taiwan, Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, Taiwan, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei 100, Taiwan and Graduate Institute of Clinical Genomics, College of Medicine, National Taiwan University, Taipei 100, Taiwan.

Abstract

The LIM homeobox 2 transcription factor Lhx2 is known to control crucial aspects of neural development in various species. However, its function in human neural development is still elusive. Here, we demonstrate that LHX2 plays a critical role in human neural differentiation, using human embryonic stem cells (hESCs) as a model. In hESC-derived neural progenitors (hESC-NPs), LHX2 was found to be expressed before PAX6, and co-expressed with early neural markers. Conditional ectopic expression of LHX2 promoted neural differentiation, whereas disruption of LHX2 expression in hESCs significantly impaired neural differentiation. Furthermore, we have demonstrated that LHX2 regulates neural differentiation at two levels: first, it promotes expression of PAX6 by binding to its active enhancers, and second, it attenuates BMP and WNT signaling by promoting expression of the BMP and WNT antagonist Cerberus 1 gene (CER1), to inhibit non-neural differentiation. These findings indicate that LHX2 regulates the transcription of downstream intrinsic and extrinsic molecules that are essential for early neural differentiation in human.

PMID:
23804753
PMCID:
PMC3763550
DOI:
10.1093/nar/gkt567
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center