Novel cuproptosis-related prognostic gene profiles in preeclampsia.

BACKGROUND: Preeclampsia (PE) is a pregnancy-specific disorder with complex pathogenesis. Cuproptosis is a novel identified form of programmed cell death, however, the link between cuproptosis and clinical outcomes in PE is still not fully understood. In this study, we searched for cuproptosis-related genes (CRGs) in the placental tissues of normal and PE patients to clarify the importance of cuproptosis in the development of PE and provide potential predictive indicators for the occurrence of PE. METHODS: Using RNA sequencing data in the GEO database, we conducted functional enrichment analysis of Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA), supported by linear regression model and operating characteristic curve (ROC) curve analysis, and summarized the role of CRGs in preeclampsia. RESULTS: A total of 2831 differentially expressed genes related to PE were screened through multiple database analyses. After further intersection with 19 reported CRGs, 5 CRGs have been closely associated with the pathogenesis of PE, including NFE2L2, PDHA1, PDHB, DLD and GLS. NFE2L2 was identified as a key central gene. Pearson correlation analysis showed that CRGs could be related to several maternal and fetal outcome factors, including the highest pregnancy blood pressure, placenta weight, umbilical blood flow pulsatility index (PI), and neonatal weight. Linear regression equation revealed that the expression of NFE2L2 is negatively correlated with the highest pregnancy blood pressure and umbilical blood flow PI but positively correlated with placental weight and neonatal weight. QRT-PCR showed that the expression of these CRGs was significantly lower in placental tissues. CONCLUSIONS: This cuproptosis pattern may be a potential prognostic factor in patients with PE and could provide new insights into disease progression.

Changing microbiome community structure and functional potential during permafrost thawing on the Tibetan Plateau.

Large amounts of carbon sequestered in permafrost on the Tibetan Plateau (TP) are becoming vulnerable to microbial decomposition in a warming world. However, knowledge about how the responsible microbial community responds to warming-induced permafrost thaw on the TP is still limited. This study aimed to conduct a comprehensive comparison of the microbial communities and their functional potential in the active layer of thawing permafrost on the TP. We found that the microbial communities were diverse and varied across soil profiles. The microbial diversity declined and the relative abundance of Chloroflexi, Bacteroidetes, Euryarchaeota, and Bathyarchaeota significantly increased with permafrost thawing. Moreover, warming reduced the similarity and stability of active layer microbial communities. The high-throughput qPCR results showed that the abundance of functional genes involved in liable carbon degradation and methanogenesis increased with permafrost thawing. Notably, the significantly increased mcrA gene abundance and the higher methanogens to methanotrophs ratio implied enhanced methanogenic activities during permafrost thawing. Overall, the composition and functional potentials of the active layer microbial community in the Tibetan permafrost region are susceptible to warming. These changes in the responsible microbial community may accelerate carbon degradation, particularly in the methane releases from alpine permafrost ecosystems on the TP.

Downregulated DUXAP8 lncRNA impedes trophoblast cell proliferation and migration by epigenetically upregulating TFPI2 expression.

BACKGROUND: Preeclampsia (PE), a pregnancy complication characterized by new-onset hypertension and proteinuria during the second trimester, is the leading cause of neonatal and maternal morbidity and mortality. In the etiology of PE, failure of uterine spiral artery remodeling may be related to functioning abnormally of trophoblast cells, leading to the occurrence and progression of PE. Recently, long noncoding RNAs (lncRNAs) have been reported to play critical roles in PE nowadays. This study aimed to investigate the expression and functions of the TFPI2 pathway-related lncRNA DUXAP8. METHODS: DUXAP8 expression in the placenta from pregnancies was examined using qPCR. Then, the in vitro functions of DUXAP8 were investigated through MTT, EdU, colony, transwell, and flow cytometry experiments. The downstream gene expression profiles were assessed using RNA transcriptome sequencing analysis and verified using qPCR and western blot. Furthermore, Immunoprecipitation (RIP), chromatin immunoprecipitation (CHIP) and fluorescence in situ hybridization (FISH) were used to detect the interaction between lncDUXAP8/EZH2/TFPI2. RESULTS: The expression of lncRNA DUXAP8 in placenta of patients with eclampsia was significantly decreased. After knockout of DUXAP8, the proliferation and migration of trophoblasts were significantly decreased, and the percentage of apoptosis was increased. Flow cytometry showed that low expression of DUXAP8 increased the accumulation of cells in G2/M phase, while overexpression of DUXAP8 had the opposite effect. We also proved that DUXAP8 epigenetically inhibited TFPI2 expression by recruiting EZH2 and mediating H3K27me3 modification. CONCLUSION: Together, these resulting data clarify that aberrant expression of DUXAP8 is involved in the potential PE development and progress. Unraveling the role of DUXAP8 will provide novel insights into the pathogenesis of PE.

IGF2BP2 enhances LincRNA01116 stability via m6 A: A potential biomarker and therapeutic target for patients with pre-eclampsia.

Pre-eclampsia (PE) is a serious complication in pregnant women characterized by failure of placental remodeling and is one of the primary causes of changes in the placental structure and function. The aberrant expression of long noncoding RNA is associated with the occurrence and progression of PE. This study found that linc01116 expression was significantly downregulated in PE patients and was related to poor uterine spiral artery remodeling. Knockdown of linc01116 remarkably decreased the angiogenesis of trophoblast cells in vitro and in vivo. Mechanistically, IGF2BP2 regulated linc01116 RNA stability via m6 A methylation. Bioinformatics and other experiments further revealed that linc01116 upregulates AAMP expression by adsorbing miR-210-3p in trophoblast cells. In conclusion, this study revealed the critical role of linc01116 in regulating trophoblast angiogenesis. Furthermore, the study provides new clues for detecting placental pathology in PE.

A novel regulatory mechanism network mediated by lncRNA TUG1 that induces the impairment of spiral artery remodeling in preeclampsia.

Preeclampsia (PE) is associated with maternal and fetal perinatal morbidity and mortality, which brings tremendous suffering and imposes an economic burden worldwide. The failure of uterine spiral artery remodeling may be related to the abnormal function of trophoblasts and lead to the occurrence and progression of PE. Aberrant expression of long non-coding RNAs (lncRNAs) is involved in the failure of uterine spiral artery remodeling. However, the regulation of lncRNA expression in PE is poorly characterized. Here, we reported that hypoxia-induced microRNA (miR)-218 inhibited the expression of lncRNA TUG1 by targeting FOXP1. Further RNA sequencing and mechanism analysis revealed that silencing of TUG1 increased the expression of DNA demethylase TET3 and proliferation-related DUSP family, including DUSP2, DUSP4, and DUSP5, via binding to SUV39H1 in the nucleus. Moreover, TUG1 modulated the DUSP family in vitro through a TET3-mediated epigenetic mechanism. Taken together, our results unmask a new regulatory network mediated by TUG1 as an essential determinant of the pathogenesis of PE, which regulates cell growth and possibly the occurrence and development of other diseases.

HHLA2 Activates the JAK/STAT Signaling Pathway by Binding to TMIGD2 in Hepatocellular Carcinoma Cells.

HHLA2, a member of the B7 family of immune checkpoint players, has been implicated in various cancers. The study set to determine the expression and biological function of HHLA2 in hepatocellular carcinoma (HCC), and its connection to TMIGD2. First, after HHLA2 knockdown or overexpression in Huh-7 or HepG2 cells, we co-cultured T cells with HCC cells after transfection for 48 h. T cell proliferation and cytokine release were detected using flow cytometry and the FlowCytomix assay kit. Subsequently, we screened differentially expressed genes in cells overexpressing or under-expressing HHLA2 using GSEA database and analyzed the pathways enriched by them. We further detected the nuclear translocation of STAT3 and STAT2 using immunofluorescence. After that, we observed the subcellular localization of HHLA2 and TMIGD2 in HCC cells by laser confocal microscopy, followed by RIP and rescue experiments. We found that the proliferation of T cells and the release of cytokines were significantly reduced after co-culture with HCC cells overexpressing HHLA2, while co-culture with cells low in HHLA2 expression had the opposite results. HHLA2 bound to TMIGD2, thus inhibiting T cell proliferation and activation. Overexpression of HHLA2 significantly promoted the nuclear translocation of STAT2 and STAT3, thereby activating the JAK/STAT pathway. Subsequently, we showed that the immune tolerance of HCC cells was significantly attenuated after using a JAK/STAT signaling pathway antagonist. Aberrant overexpression of HHLA2 activates the JAK/STAT signaling pathway by binding to TMIGD2, thereby promoting immune tolerance in HCC cells.

Maternal and neonatal outcomes of repeated antepartum bleeding in 493 placenta previa cases: a retrospective study.

OBJECTIVE: To explore the effect of antepartum bleeding caused by PP on pregnancy outcomes. STUDY DESIGN: We retrospectively analyzed 493 pregnant women complicated with PP. Patients were divided into antepartum repeated bleeding and non-bleeding groups. Maternal characteristics and pregnancy outcomes were compared. RESULTS: The risk of antepartum hemorrhage was 2.038 times higher when gravidity was 5 (95% CI 1.104-3.760, p = .023). Pregnant women with a history of more than three intrauterine procedures had a 1.968 times higher risk of antepartum hemorrhage (95% CI 1.135-3,412, p = .016) compared to pregnant women without any intrauterine procedures. The risk of antepartum bleeding was found to be decreasing with the pregnancy advancing; When the placenta edge was noted to be over cervical os, the risk of antepartum bleeding was 4.385-fold than the low-lying plcaenta cases (95%CI2.454-8.372, p = .000). In the respect of maternal outcomes, the repeated bleeding group, the risk of emergency surgery was 7.213 times higher than elective surgery (95% CI 4.402-11.817, p = .000). As for the neonatal outcomes, the risk of asphyxia was 2.970 times and the risk of neonatal intensive care unit (NICU) admission was 2.542-fold higher in repeated bleeding group compared to non-bleeding group, respectively. CONCLUSIONS: Obstetricians should be aware of the increased risk of antepartum bleeding especially for ≤34 weeks and placenta edge over cervical os PP patients, they have a higher risk of antepartum bleeding. These women have higher possibility of emergency C-section and need preterm newborn resuscitation.

Interferon Gamma-Induced Interferon Regulatory Factor 1 Activates Transcription of HHLA2 and Induces Immune Escape of Hepatocellular Carcinoma Cells.

Immunosuppression developed by cancer cells remains a leading cause of treating failure of immunotherapies. This study aimed to explore the function of human endogenous retrovirus-H long terminal repeat-associating 2 (HHLA2), an immune checkpoint molecule from the B7 family, in the immune escape in hepatocellular carcinoma (HCC). Mouse models with primary HCC or with xenograft tumors were established. The portion of tumor-associated macrophages (TAMs) and the level of PD-L1 in the tumor tissues were examined. THP-1 cells were treated with PMA to obtain a macrophage-like phenotype. The PMA-treated THP-1 cells were co-cultured with the HCC cells in Transwell chambers to examine the function of HHLA2 in chemotactic migration and polarization of macrophages. HHLA2 expression was correlated with infiltration of immune cells, especially macrophages, and was linked to poor prognosis of patients with HCC. HHLA2 knockdown reduced incidence rate of primary HCC in mice. It also reduced tumor metastasis, the portion of M2 macrophages, and the expression of PD-L1 in primary and xenograft tumors. In vitro, HHLA2 upregulation increased expression of PD-L1 in HCC cells indirectly by inducing M2 polarization and chemotactic migration of macrophages. Interferon gamma (IFNG) enhanced expression of interferon regulatory factor 1 (IFR1) in HCC cells, and IFR1 bound to the promoter region of HHLA2 to activate HHLA2 expression. This study suggested that the IFNG/IFR1/HHLA2 axis in HCC induces M2 polarization and chemotactic migration of macrophages, which leads to immune escape and development of HCC.

Silencing of AFAP1-AS1 lncRNA impairs cell proliferation and migration by epigenetically promoting DUSP5 expression in pre-eclampsia.

As a unique and common obstetric complication of pregnant women, pre-eclampsia (PE) has been the first leading cause of maternal and perinatal morbidity and mortality in the world. Mounting studies have demonstrated that an abnormality of long noncoding RNA (lncRNA) expression was related to the pathological process of PE. Here, we showed that lncRNA AFAP1-AS1 was markedly downregulated in pre-eclamptic placentas. We further investigated the mechanism underlying the regulatory role of AFAP1-AS1 in PE using human trophoblast cells. In vitro functional assays revealed that AFAP1-AS1 knockdown inhibited trophoblast proliferation, migration, and invasion. Moreover, AFAP1-AS1 interacts with EZH2 and inhibits DUSP5 expression through modulating H3K27m3 in the DUSP5 promoter of trophoblast cells, thus being involved in PE pathogenesis. Overall, these findings suggest that AFAP1-AS1 could potentially become a prognostic biomarker as well as a new therapeutic target for PE.

ZhiShiXiaoPi tang inhibits autophagy induced by corticosterone and functional dyspepsia through blockade of the mTOR pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: ZhiShiXiaoPi Tang (ZSXPT) is a Chinese traditional medicine formula that contains 10 Chinese traditional medicine substances. It has been widely used to treat patients with functional dyspepsia (FD). However, the protective effect of ZSXPT and its molecular mechanisms in FD still remain elusive. AIM OF THE STUDY: To investigate the protective effect of ZSXPT on autophagy induced by Corticosterone (Cort) in PC12 cells which have typical neuron characteristics and have been widely used as a model system for depression studies and FD rats, and explore its underlying mechanisms. MATERIALS AND METHODS: In this study, high-performance liquid chromatography fingerprint analysis was performed to characterize the chemical composition of ZSXPT. Depression-induced autophagy, ROS generation, and changes in mitochondrial membrane potential (MMP) were investigated in Cort-induced PC12 cells and in FD rats to evaluate the protective effects of ZSXPT. RESULTS: Our results show that ZSXPT treatment protects neurons against Cort-induced damage and apoptosis by increasing cell viability and reducing the release of lactate dehydrogenase. ZSXPT decreased Cort-induced ROS generation, increased MMP, and accelerated autophagy through the blockade of the mammalian target of rapamycin (mTOR) pathway. Moreover, we observed similar findings when we studied ZSXPT in a rat model of FD. CONCLUSIONS: Our in vitro and in vivo results indicate that the neuroprotective effect of ZSXPT against autophagy-induced damage and apoptosis occurs mainly by blocking the mTOR pathway in Cort-induced PC12 cells and in FD rats. Taken together, these data provide reliable experimental evidence and explain the molecular mechanism by which ZSXPT ameliorates FD.

Electrospinning Preparation of La-Doped SnO2 Hollow Nanofibers: An Improvement of Their Gas Sensing Properties.

SnO2 hollow nanofibers with different amount of La-doped were prepared by electrostatic spinning method. Their composition, morphology and structure were characterized by XRD, SEM, BET and XPS respectively and their gas sensing properties were also investigated. The results showed that the hollow nanofibers with the molar ratio of tin to La of 7% had the best sensitivity to ammonia of 500 ppm at the temperature of 300 °C, and the sensitivity value reached 480, which was 10 times that of pure SnO2. And its response time was also significantly shortened.

Liver X receptor ß regulates the development of the dentate gyrus and autistic-like behavior in the mouse.

The dentate gyrus (DG) of the hippocampus is a laminated brain region in which neurogenesis begins during early embryonic development and continues until adulthood. Recent studies have implicated that defects in the neurogenesis of the DG seem to be involved in the genesis of autism spectrum disorders (ASD)-like behaviors. Liver X receptor ß (LXRß) has recently emerged as an important transcription factor involved in the development of laminated CNS structures, but little is known about its role in the development of the DG. Here, we show that deletion of the LXRß in mice causes hypoplasia in the DG, including abnormalities in the formation of progenitor cells and granule cell differentiation. We also found that expression of Notch1, a central mediator of progenitor cell self-renewal, is reduced in LXRß-null mice. In addition, LXRß deletion in mice results in autistic-like behaviors, including abnormal social interaction and repetitive behavior. These data reveal a central role for LXRß in orchestrating the timely differentiation of neural progenitor cells within the DG, thereby providing a likely explanation for its association with the genesis of autism-related behaviors in LXRß-deficient mice.

Estrogen modulation of calretinin and BDNF expression in midbrain dopaminergic neurons of ovariectomised mice.

Estrogen attenuates the loss of dopamine neurons from the substantia nigra in animal models of Parkinson's disease (PD) and excitatory amino-acid induced neurotoxicity by interactions with brain-derived neurotrophic factor (BDNF), and calretinin (CR) containing dopaminergic (DA) neurons. To examine this interaction more closely, we treated the ovariectomised (OVX) mice with estrodial for 10days, and compared these mice to those OVX mice injected with the vehicle or control mice. Estrogen treatment in OVX mice had significantly more tyrosine hydroxylase (TH) positive neurons in the substantia nigra pars compacta (SNpc). Dopamine transporter (DAT) mRNA and BDNF mRNA levels in the midbrain were also significantly increased by estrogen treatment (P<0.05). OVX markedly decreased the number of TH/CR double stained cells in the SNpc (P<0.05), a trend which could be reversed by estrogen treatment. However, the number of GFAP positive cells in the substantia nigra did not show significant changes (P >0.05) after vehicle or estrodial treatment. Furthermore, we found that estrogen treatment abrogated the OVX-induced decrease in the phosphorylated AKT (p-AKT), but not p-ERK. We hypothesize that short-term treatment with estrogen confers neuroprotection to DA neurons by increasing CR in the DA neurons and BDNF in the midbrain, which possibly related to activation of the PI3K/Akt signaling pathway.

Radial glia, the keystone of the development of the hippocampal dentate gyrus.

The morphogenesis of the dentate gyrus (DG) of the hippocampus primarily occurs postnatally, and the DG is one of the few regions of continuous neurogenesis in the adult brain. Radial glial cells (RGCs), which contribute to DG development by participating in key steps of morphogenesis, are maintained in the subgranular zone (SGZ), where they play pivotal roles in adult hippocampal neurogenesis. It is clear that a series of molecules control the development of RGCs, thereby regulating the morphogenesis of the DG and neurogenesis in the adult hippocampus. In this review, we provide an updated framework regarding the molecular mechanisms involved in the development of RGCs during DG morphogenesis and discuss the key steps that regulate DG formation.

Liver X receptor ß delays transformation of radial glial cells into astrocytes during mouse cerebral cortical development.

Radial glial (RG) cells serve as stem cells to produce new born neurons and scaffolds for neuronal migration during corticogenesis. After neurogenesis and migration are completed, most RG cells transform into astrocytes. However, the mechanisms that determine how RG cells are transformed into astrocytes are not well understood. Using nestin as a specific marker for both RG cells and astrocytes, we found that loss of LXRß caused a reduction in the level of RG fibers and increase in the astrocytes. At the same time, we showed that the level of brain lipid-binding protein (BLBP), a RG-specific protein, was lower in the LXRß knockout (LXRß(-/-)) mice than in the wild type (WT) littermates from E18.5 to P14, a time period when most of RG cells are transformed into astrocytes. However, loss of LXRß induced significant increase in the number of GFAP labeled astrocytes in the cerebral cortex. An increase of the transformation of RG cells into astrocytes in LXRß(-/-) mice was further confirmed by the increased percentage of BLBP and GFAP double stained cells in the total BLBP positive cells of the Layer I and Layers V-VI. TGF-ß1 and Smad4 are thought to be involved in the transformation of RG cells into astrocytes. The expression levels of TGF-ß1mRNA and Smad4 mRNA were significantly higher in the cerebral cortex of LXRß(-/-) mice than that in the WT littermates at P2 and P7, but by P10 and P14, mRNA levels had normalized and no differences were observed between WT and LXRß(-/-) mice. Taken together, our findings suggest that loss of LXRß accelerates the transformation of RG cells into astrocytes and that this acceleration may be correlated to higher levels TGF-ß1 and Smad4 in the cerebral cortex between P2 and P7.

Stem-cell challenges in the treatment of Alzheimer's disease: a long way from bench to bedside.

Alzheimer's disease (AD) is the most prevalent type of dementia, and its neuropathology is characterized by deposition of insoluble ß-amyloid peptides, intracellular neurofibrillary tangles, and the loss of diverse neurons. Current pharmacological treatments for AD relieve symptoms without affecting the major pathological characteristics of the disease. Therefore, it is essential to develop new and effective therapies. Stem-cell types include tissue-specific stem cells, such as neural stem cells and mesenchymal stem cells, embryonic stem cells derived from blastocysts, and induced pluripotent stem cells (iPSCs) reprogrammed from somatic cells. Recent preclinical evidence suggests that stem cells can be used to treat or model AD. The mechanisms of stem cell based therapies for AD include stem cell mediated neuroprotection and trophic actions, antiamyloidogenesis, beneficial immune modulation, and the replacement of the lost neurons. iPSCs have been recently used to model AD, investigate sporadic and familial AD pathogenesis, and screen for anti-AD drugs. Although considerable progress has been achieved, a series of challenges must be overcome before stem cell based cell therapies are used clinically for AD patients. This review highlights the recent experimental and preclinical progress of stem-cell therapies for AD, and discusses the translational challenges of their clinical application.

Activation of liver X receptor is protective against ethanol-induced developmental impairment of Bergmann glia and Purkinje neurons in the mouse cerebellum.

Cerebellar Purkinje cell and granule cell development are coordinated by Bergmann glia, and are particularly sensitive to ethanol (EtOH) exposure. The liver X receptor (LXR) plays important roles in Bergmann glial development. However, the effect of LXR activation on EtOH-mediated impairment of Bergmann glia and subsequently on Purkinje cell dendritogenesis remains undetermined. Therefore, using immunohistochemistry, quantitative real-time PCR and Western blot, we tested the possible protection of LXR agonist T0901317 (T0) on Bergmann glia and Purkinje cell dendritogenesis in mice exposed to ethanol. Results showed that a brief exposure of EtOH on postnatal day (PD 5) significantly decreased the average body weight of mice at PD 6 without alteration in the brain weight. In EtOH-exposed mice, the number of migrating granule cells in the molecular layer was significantly decreased, and this effect was attenuated by pretreatment of T0. EtOH exposure also resulted in the significant reduction of calbindin-labeled Purkinje cells, their maximum dendrite length, and impairment of Purkinje cell dendritogenesis. Furthermore, EtOH induced the activation of microglia in the Purkinje cell layer and impaired the development of Bergmann glia. However, pretreatment of T0 effectively blocked all of these responses. These responses were found to be mediated by the inhibition of upregulated levels of ß-catenin and transcription factor LEF1 in the cerebellum. Overall, the results suggest that activating LXRs on postnatal mice exposed to EtOH is protective to Bergmann glia, and thus may play a critical role in preventing EtOH-induced defects during cerebellar development.

LXR agonists: new potential therapeutic drug for neurodegenerative diseases.

Liver X receptors (LXRs) are nuclear receptors involved in the regulation of lipid metabolism and inflammatory responses in the central nervous system. Defects in cholesterol homeostasis contribute to the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and Huntington's disease. Inflammatory responses could enhance the neurodegenerative process or act independently. The natural and synthetic LXR agonists induce the transcriptional activity of LXR target genes, thus attenuate the imbalance of cholesterol metabolism and overactivation of microglia and astrocytes in inflammation and are widely used in a variety of neurodegenerative diseases animal models. By developing more specific, potent, penetrable, and functional LXR agonist may lead to a better curative effect for neurodegenerative diseases and avoidance of potentially deleterious side effects. Here, we focus on recent advances in our understanding of the role of LXRs and their agonists in cholesterol homeostasis, inflammation, and the potential therapeutic effects in neurodegenerative diseases.

Bergmann glia function in granule cell migration during cerebellum development.

Granule cell migration influences the laminar structure of the cerebellum and thereby affects cerebellum function. Bergmann glia are derived from radial glial cells and aid in granule cell radial migration by providing a scaffold for migration and by mediating interactions between Bergmann glia and granule cells. In this review, we summarize Bergmann glia characteristics and the mechanisms underlying the effect of Bergmann glia on the radial migration of granule neurons in the cerebellum. Furthermore, we will focus our discussion on the important factors involved in glia-mediated radial migration so that we may elucidate the possible mechanistic pathways used by Bergmann glia to influence granule cell migration during cerebellum development.

ERß may contribute to the maintaining of radial glia cells polarity through cadherins during corticogenesis.

Laminar organization of neurons in cerebral cortex is essential for normal brain function. Radial glial cells (RGCs), are highly polarized cells that serve as neuronal progenitors and as scaffolds for neuronal migration during construction of the cerebral cortex. Cadherins (E-cadherin and N-cadherin)-based adherins junctions, which anchor apical end-feet of adjacent RGCs to each other at the ventricular surface contribute to sustain the polarity and adhesion of RGCs, therefore affect production of RGCs and radial migration. Estrogen is a steroid hormone and contributes to the organizational sexual differentiation of the brain. We have previously demonstrated that ERß expression in the cerebral cortex during corticogenesis and contribute to cerebral cortex development. This has been further confirmed by studies from estrogen receptor ß knockout (ERßKO) mice, in which lack of ERß in mice induced abnormal development of cerebral cortical structure, retarded migration of the neurons, and abnormal morphology of RGCs with truncated or less organized radial processes. These indicate that estrogen via ERß affects RGCs development. Moreover, phenotype analysis in the ERßKO mice has confirmed that estrogen activation ERß influence the polarity of epithelial tissue and structure integrity by modulating the level of cadherins (E-cadherin and N-cadherin). Thus, we propose that ERß maybe affect the maintaining the polarity of RGCs through cadherins.