| 1 | PLoS ONE 2013 -1 8: e73169 |
|---|---|
| PMID | 24058414 |
| Title | Knockdown of human TCF4 affects multiple signaling pathways involved in cell survival, epithelial to mesenchymal transition and neuronal differentiation. |
| Abstract | Haploinsufficiency of TCF4 causes Pitt-Hopkins syndrome (PTHS): a severe form of mental retardation with phenotypic similarities to Angelman, Mowat-Wilson and Rett syndromes. Genome-wide association studies have also found that common variants in TCF4 are associated with an increased risk ofschizophrenia。Although TCF4 is transcription factor, little is known about TCF4-regulated processes in the brain. In this study we used genome-wide expression profiling to determine the effects of acute TCF4 knockdown on gene expression in SH-SY5Y neuroblastoma cells. We identified 1204 gene expression changes (494 upregulated, 710 downregulated) in TCF4 knockdown cells. Pathway and enrichment analysis on the differentially expressed genes in TCF4-knockdown cells identified an over-representation of genes involved in TGF-? signaling, epithelial to mesenchymal transition (EMT) and apoptosis. Among the most significantly differentially expressed genes were the EMT regulators, SNAI2 and DEC1 and the proneural genes, NEUROG2 and ASCL1. Altered expression of several mental retardation genes such as UBE3A (Angelman Syndrome),ZEB2(Mowat-Wilson Syndrome) and MEF2C was also found in TCF4-depleted cells. These data suggest that TCF4 regulates a number of convergent signaling pathways involved in cell differentiation and survival in addition to a subset of clinically important mental retardation genes. |
| SCZ关键字 | schizophrenia |
| 2 | Schizophr. Res. 2016 Mar -1: -1 |
| PMID | 26972474 |
| Title | 精神分裂症前额叶皮质中类蛋白酶和生长抑素神经元的发育调节剂的表达改变。 |
| Abstract | 前额叶皮层（PFC）抑制性神经元的功能障碍，该神经元表达钙结合蛋白白蛋白或神经肽生长抑素在schizophreniamay be related to disturbances in the migration, phenotypic specification, and/or maturation of these neurons. These pre- and postnatal developmental stages are regulated in a cell type-specific manner by various transcription factors and co-activators, fibroblast growth factor receptors (FgfR), and other molecular markers. Consequently, we used quantitative PCR to quantify mRNA levels for these developmental regulators in the PFC of 62schizophreniasubjects in whom parvalbumin and somatostatin neuron disturbances were previously reported, and in antipsychotic-exposed monkeys. Relative to unaffected comparison subjects, subjects withschizophreniaexhibited elevated mRNA levels for 1) the transcription factor MafB, which is expressed by parvalbumin and somatostatin neurons as they migrate from the medial ganglionic eminence to the cortex, 2) the transcriptional coactivator PGC-1?, which is expressed postnatally by parvalbumin neurons to maintain parvalbumin levels and inhibitory function, and 3) FgfR1, which is required for the migration and phenotypic specification of parvalbumin and somatostatin neurons. Elevations in these markers were most prominent in youngerschizophreniasubjects and were not present in antipsychotic-exposed monkeys. Finally, expression levels of other important developmental regulators (i.e. Dlx1, Dlx5, Dlx6, SATB1, Sip1/ZEB2, ST8SIA4, cMaf, Nkx6.2, and Arx) were not altered inschizophrenia。The over-expression of a subset of molecular markers with distinct roles in the pre- and postnatal development of parvalbumin and somatostatin neurons might reflect compensatory mechanisms to sustain the development of these neurons in the face of other insults. |
| SCZ关键字 | schizophrenia |
| 3 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2016 Apr 66: 97-103 |
| PMID | 26654950 |
| Title | A new risk locus in the ZEB2 gene for schizophrenia in the Han Chinese population. |
| Abstract | TheZEB2gene encodes the Zinc Finger E-box binding protein. As a key regulator of epithelial mesenchymal differentiation,ZEB2plays an important role in the pathogenesis of cancer, and its high level expression has been observed in glioma patients. Different mutations in this gene have been identified in patients with Mowat-Wilson syndrome. A previous genome-wide association study (GWAS) ofschizophrenia在高加索人进行的ZEB2gene, withschizophrenia。因此，我们进行了一项案例控制研究，以进一步研究该基因组区域是否也是对schizophreniain the Han Chinese population. In total, 1248schizophrenia(SCZ) cases (mean age�S.D., 36.44�9.0years), 1344 bipolar disorder (BPD) cases (mean age�S.D., 34.84�11.44years), 1056 major depressive disorder (MDD) cases (mean age�S.D., 34.41�12.09years) and 1248 healthy control samples (mean age�S.D., 30.62�11.35years) were recruited. We genotyped 12 SNPs using the Sequenom MassARRAY platform in this study. We found that rs6755392 showed a significant association with SCZ (rs6755392: adjusted Pallele=0.016; adjusted Pgenotype=0.052; OR (95% CI)=1.201 (1.073~1.344)). Additionally, two haplotypes (TCTG, TCTA) were also significantly associated with SCZ. This is the first study claiming the association of the genetic risks of rs6755392 in theZEB2gene withschizophrenia。 |
| SCZ关键字 | schizophrenia |