Empty Spiracles Research Articles

Formation and subdivision of the head field in the centipede Strigamia maritima, as revealed by the expression of head gap gene orthologues and hedgehog dynamics

BackgroundThere have been few studies of head patterning in non-insect arthropods, and even in the insects, much is not yet understood. In the fly Drosophila three head gap genes, orthodenticle (otd), buttonhead (btd) and empty spiracles (ems) are essential for patterning the head. However, they do not act through the same pair-rule genes that pattern the trunk from the mandibular segment backwards. Instead they act through the downstream factors collier (col) and cap‘n’collar (cnc), and presumably other unknown factors. In the beetle Tribolium, these same gap and downstream genes are also expressed during early head development, but in more restricted domains, and some of them have been shown to be of minor functional importance. In the spider Parasteatoda tepidariorum, hedgehog (hh) and otd have been shown to play an important role in head segmentation.ResultsWe have investigated the expression dynamics of otx (otd), SP5/btd, ems, and the downstream factors col, cnc and hh during early head development of the centipede Strigamia maritima. Our results reveal the process of head condensation and show that the anteroposterior sequence of specific gene expression is conserved with that in insects. SP5/btd and otx genes are expressed prior to and during head field formation, whereas ems is not expressed until after the initial formation of the head field, in an emerging gap between SP5/btd and otx expression. Furthermore, we observe an early domain of Strigamia hh expression in the head field that splits to produce segmental stripes in the ocular, antennal and intercalary segments.ConclusionsThe dynamics of early gene expression in the centipede show considerable similarity with that in the beetle, both showing more localised expression of head gap genes than occurs in the fly. This suggests that the broad overlapping domains of head gap genes observed in Drosophila are derived in this lineage. We also suggest that the splitting of the early hh segmental stripes may reflect an ancestral and conserved process in arthropod head patterning. A remarkably similar stripe splitting process has been described in a spider, and in the Drosophila head hh expression starts from a broad domain that transforms into three stripes.

EMX2 gene expression predicts liver metastasis and survival in colorectal cancer

BackgroundThe Empty Spiracles Homeobox (EMX-) 2 gene has been associated with regulation of growth and differentiation in neuronal development. While recent studies provide evidence that EMX2 regulates tumorigenesis of various solid tumors, its role in colorectal cancer remains unknown. We aimed to assess the prognostic significance of EMX2 expression in stage III colorectal adenocarcinoma.MethodsExpression levels of EMX2 in human colorectal cancer and adjacent mucosa were assessed by qRT-PCR technology, and results were correlated with clinical and survival data. siRNA-mediated knockdown and adenoviral delivery-mediated overexpression of EMX2 were performed in order to investigate its effects on the migration of colorectal cancer cells in vitro.ResultsCompared to corresponding healthy mucosa, colorectal tumor samples had decreased EMX2 expression levels. Furthermore, EMX2 down-regulation in colorectal cancer tissue was associated with distant metastasis (M1) and impaired overall patient survival. In vitro knockdown of EMX2 resulted in increased tumor cell migration. Conversely, overexpression of EMX2 led to an inhibition of tumor cell migration.ConclusionsEMX2 is frequently down-regulated in human colorectal cancer, and down-regulation of EMX2 is a prognostic marker for disease-free and overall survival. EMX2 might thus represent a promising therapeutic target in colorectal cancer.

Empty Spiracles Homeobox 2 (EMX2) Inhibits the Invasion and Tumorigenesis in Colorectal Cancer Cells.

Empty spiracles homeobox 2 (EMX2) is a homeodomain-containing transcription factor that plays an essential role in tumorigenesis. However, to the best of our knowledge, the role of EMX2 in human colorectal cancer (CRC) is still unclear. Thus, the aim of this study was to investigate the expression and role of EMX2 in CRC. Our results demonstrated that the expression of EMX2 was greatly decreased in CRC tissues and cell lines. Overexpression of EMX2 significantly inhibited the proliferation in vitro and CRC tumor growth in nude mice. In addition, EMX2 also inhibited the migration and invasion of CRC cells. Mechanically, overexpression of EMX2 downregulated the expression levels of β-catenin, cyclin D1, and c-Myc in CRC cells. Taken together, our study demonstrates that EMX2 inhibits proliferation and tumorigenesis through inactivation of the Wnt/β-catenin pathway in CRC cells. Therefore, EMX2 may be a potential therapeutic target for the treatment of CRC.

Transcriptional Timers Regulating Mitosis in Early Drosophila Embryos

The development of an embryo requires precise spatiotemporal regulation of cellular processes. During Drosophila gastrulation, a precise temporal pattern of cell division is encoded through transcriptional regulation of cdc25(string) in 25 distinct mitotic domains. Using a genetic screen, we demonstrate that the same transcription factors that regulate the spatial pattern of cdc25(string) transcription encode its temporal activation. We identify buttonhead and empty spiracles as the major activators of cdc25(string) expression in mitotic domain 2. The effect of these activators is balanced through repression by hairy, sloppy paired 1, and huckebein. Within the mitotic domain, temporal precision of mitosis is robust and unaffected by changing dosage of rate-limiting transcriptional factors. However, precision can be disrupted by altering the levels of the two activators or two repressors. We propose that the additive and balanced action of activators and repressors is a general strategy for precise temporal regulation of cellular transitions during development.

Regulation of twin of eyeless during Drosophila development

The Pax-6 protein is vital for eye development in all seeing animals, from sea urchins to humans. Either of the Pax6 genes in Drosophila (twin of eyeless and eyeless) can induce a gene cascade leading to formation of entire eyes when expressed ectopically. The twin of eyeless (toy) gene in Drosophila is expressed in the anterior region of the early fly embryo. At later stages it is expressed in the brain, ventral nerve cord and (eventually) the visual primordium that gives rise to the eye-antennal imaginal discs of the larvae. These discs subsequently form the major part of the adult head, including compound eyes. We have searched for genes that are required for normal toy expression in the early embryo to elucidate initiating events of eye organogenesis. Candidate genes identified by mutation analyses were subjected to further knock-out and miss-expression tests to investigate their interactions with toy. Our results indicate that the head-specific gap gene empty spiracles can act as a repressor of Toy, while ocelliless (oc) and spalt major (salm) appear to act as positive regulators of toy gene expression.

Differential gene expression patterns during embryonic development of sea urchin exposed to triclosan.

Triclosan (TCS; 2,4,4'-trichloro-2'-hydroxydiphenyl ether) is a broad-spectrum antibacterial agent used in common industrial, personal care and household products which are eventually rinsed down the drain and discharged with wastewater effluent. It is therefore commonly found in the aquatic environment, leading to the continual exposure of aquatic organisms to TCS and the accumulation of the antimicrobial and its harmful degradation products in their bodies. Toxic effects of TCS on reproductive and developmental progression of some aquatic organisms have been suggested but the underlying molecular mechanisms have not been defined. We investigated the expression patterns of genes involved in the early development of TCS-treated sea urchin Strongylocentrotus nudus using cDNA microarrays. We observed that the predominant consequence of TCS treatment in this model system was the widespread repression of TCS-modulated genes. In particular, empty spiracles homeobox 1 (EMX-1), bone morphogenic protein, and chromosomal binding protein genes showed a significant decrease in expression in response to TCS. These results suggest that TCS can induce abnormal development of sea urchin embryos through the concomitant suppression of a number of genes that are necessary for embryonic differentiation in the blastula stage. Our data provide new insight into the crucial role of genes associated with embryonic development in response to TCS. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 426-433, 2017.

HOXA10, EMX2 and TENM1 expression in the mid-secretory endometrium of infertile women with a Müllerian duct anomaly

Homeobox A10 (HOXA10) and empty spiracles homeobox 2 (EMX2) are two transcription factors necessary for female Müllerian duct differentiation and development. They are thought to play important roles in embryo implantation in mice and humans. The EMX2 gene is a known direct target of HOXA10 in the reproductive tract. Human TENM1 is directly regulated by EMX2 and is expressed during embryonic pattern formation and morphogenesis. This study aimed to investigate expression patterns of HOXA10, EMX2 and TENM1 in the mid-secretory endometrium of infertile patients with a Müllerian duct anomaly causing a partially septate uterus. Thirteen mid-secretory endometrial tissue samples were collected from women with partially septate uteri and 12 from women with normal uteri as controls. Expression levels of HOXA10, EMX2 and TENM1 mRNA and protein in the mid-secretory endometrium of infertile patients and controls were measured by quantitative reverse transcription polymerase chain reaction and western blotting. Compared with controls, mRNA and protein expression levels of HOXA10 decreased significantly (P < 0.01), whereas EMX2 and TENM1 increased dramatically in patients with Müllerian duct anomaly (P < 0.001). Changes in HOXA10, EMX2, and TENM1 expression levels might act in infertile women with Müllerian duct anomaly to cause a partially septate uterus.

Subset of early radial glial progenitors that contribute to the development of callosal neurons is absent from avian brain

The classical view of mammalian cortical development suggests that pyramidal neurons are generated in a temporal sequence, with all radial glial cells (RGCs) contributing to both lower and upper neocortical layers. A recent opposing proposal suggests there is a subgroup of fate-restricted RGCs in the early neocortex, which generates only upper-layer neurons. Little is known about the existence of fate restriction of homologous progenitors in other vertebrate species. We investigated the lineage of selected Emx2+ [vertebrate homeobox gene related to Drosophila empty spiracles (ems)] RGCs in mouse neocortex and chick forebrain and found evidence for both sequential and fate-restricted programs only in mouse, indicating that these complementary populations coexist in the developing mammalian but not avian brain. Among a large population of sequentially programmed RGCs in the mouse brain, a subset of self-renewing progenitors lack neurogenic potential during the earliest phase of corticogenesis. After a considerable delay, these progenitors generate callosal upper-layer neurons and glia. On the other hand, we found no homologous delayed population in any sectors of the chick forebrain. This finding suggests that neurogenic delay of selected RGCs may be unique to mammals and possibly associated with the evolution of the corpus callosum.

Comparative analysis of zygotic developmental genes in Rhodnius prolixus genome shows conserved features on the tracheal developmental pathway

Most of the in-depth studies on insect developmental genetic have been carried out in the fruit fly Drosophila melanogaster, an holometabolous insect, so much more still remains to be studied in hemimetabolous insects. Having Rhodnius prolixus sequenced genome available, we search for orthologue genes of zygotic signaling pathways, segmentation, and tracheogenesis in the R. prolixus genome and in three species of Triatoma genus transcriptomes, concluding that there is a high level of gene conservation. We also study the function of two genes required for tracheal system development in D. melanogaster - R. prolixus orthologues: trachealess (Rp-trh) and empty spiracles (Rp-ems). From that we see that Rp-trh is required for early tracheal development since Rp-trh RNAi shows that the primary tracheal branches fail to form. On the other hand, Rp-ems is implied in the proper formation of the posterior tracheal branches, in a similar way to D. melanogaster. These results represent the initial characterization of the genes involved in the tracheal development of an hemimetabolous insect building a bridge between the current genomic era and V. Wigglesworth's classical studies on insects' respiratory system physiology.

Identification and expression of the target gene emx2 of miR-26a and miR-26b in Paralichthys olivaceus

MicroRNAs (miRNAs) can regulate specific gene expression by binding to target mRNA further involution to diverse biological processes. Our previous miRNA sequencing showed that pol-miR-26a and pol-miR-26b have a sex-biased expression in ovary and testis of Paralichthys olivaceus (P. olivaceus). And the gene empty spiracles homeobox 2 (emx2) was proposed to be a candidate target by bioinformatics prediction. In this study, we cloned the P. olivaceus emx2 cDNA, including a coding region of 741bp and a 3′-untranslated region (UTR) of 912bp and the 5′-UTR of 12bp. The Emx2 protein is highly conserved and especially its homeodomain region is 100% identical from teleosts to mammals. Real-time PCR results showed that the emx2 is not only highly expressed in embryonic neurula stage and adult brain but also has abundant expression in adult gonad, moreover, it exhibits higher expression in ovary than testis. To determine the relationship between emx2 and miRNAs, a luciferase reporter assay was performed and verified that the emx2 is a common target gene of pol-miR-26a and pol-miR-26b. These data thus helps further clarify that miR-26a and miR-26b are involved in regulating gonad development partially through its target on emx2 expression in P. olivaceus.

Expression of empty spiracles homeobox 2 in non-small cell lung cancer and its correlation with clinicopathological features and prognosis

Objective To investigate the expression of empty spiracles homeobox 2(EMX2)and its correlation with clinicopathological features and prognosis in patients with non-small cell lung cancer (NSCLC) Methods The expression of EMX2 in 60 cases of NSCLC was detected by immunohistochemistry and reverse transcriptase-polymerase chain reaction(RT-PCR).The correlation of the expression of EMX2 with clinicopathological features and overall survival of the NSCLC patients was analyzed Results The positive expression rate of EMX2 was 78. 3%(47/60)and the median survival time was 15 months. Univariate analysis revealed that TNM stage, lymph node status and EMX2 expression were significantly associated with prognosis in the NSCLC patients(P< 0. 05).The Cox multivariate analysis demonstrated that EMX2 expression, lymph nodes status and TNM stage were independent prognostic factors(P< 0. 05). Conclusion The low expression of EMX2 in NSCLC is closely associated with poor prognosis. Key words: Non-small cell lung carcinoma; Empty spiracles homeobox 2; Prognosis

Nonsense mutation of EMX2 is potential causative for uterus didelphysis: first molecular explanation for isolated incomplete müllerian fusion

To investigate the association between human empty spiracles homeobox 2 gene (EMX2) and incomplete müllerian fusion (IMF). Case-control study. University-based hospital. Cohort of 517 clinically well-characterized IMF cases and 563 control women. None. In cases and control women, direct sequencing of EMX2 exons and further functional studies; for functional studies, wild-type and mutant EMX2 expression plasmids constructed; human embryonic kidney cells (HEK293FT) transfected with empty vector, wild-type EMX2, mutant EMX2, and 1:1 combination (wild-type/mutant plasmids) with additional functional studies performed to clarify the deleterious effect of the novel mutation detected. A novel nonsense mutation p.E142X was detected in one woman with a didelphic uterus (1 of 517, 0.19%). The results of Western blot analysis confirmed that the mutation caused a truncated protein as predicted, and functional studies proved that it resulted in a dominant negative effect. The novel nonsense mutation we detected-EMX2, p.E142X- resulted in a dominant negative effect. The functional data were exemplified in HEK293FT cells. This reinforced the likelihood that EMX2 contributed to the pathophysiology of IMF. Although it is uncommon (0.19%), EMX2 is the first gene identified that if perturbed may cause isolated IMF.

Specification of neuronal subtypes by different levels of Hunchback.

During the development of the central nervous system, neural progenitors generate an enormous number of distinct types of neuron and glial cells by asymmetric division. Intrinsic genetic programs define the combinations of transcription factors that determine the fate of each cell, but the precise mechanisms by which all these factors are integrated at the level of individual cells are poorly understood. Here, we analyzed the specification of the neurons in the ventral nerve cord of Drosophila that express Crustacean cardioactive peptide (CCAP). There are two types of CCAP neurons: interneurons and efferent neurons. We found that both are specified during the Hunchback temporal window of neuroblast 3-5, but are not sibling cells. Further, this temporal window generates two ganglion mother cells that give rise to four neurons, which can be identified by the expression of empty spiracles. We show that the expression of Hunchback in the neuroblast increases over time and provide evidence that the absolute levels of Hunchback expression specify the two different CCAP neuronal fates.

Regulation of endometrial receptivity by the highly expressed HOXA9, HOXA11 and HOXD10 HOX-class homeobox genes

Are other HOX genes, in addition to HOXA10, involved in endometrial receptivity? The highly expressed HOXA9, HOXA11 and HOXD10 genes also appear to be involved in endometrial receptivity. Within the HOX family of homeobox transcription factor genes are the leading candidates for the regulation of embryonic implantation. A crucial role of HOXA10 in endometrial receptivity has been well established. To identify HOX candidate genes, we performed data mining on all 39 human HOX genes in the 'Human body index' gene expression database of normal human tissue. The temporal and spatial expression pattern of four highly expressed HOX genes in the human endometrium was determined. To further investigate the function of these Hox genes, we used a robust in vivo mouse model in which we blocked maternal Hox gene expression. Analysis of a gene expression profile set in the public domain consisting of 504 samples representing 95 different normal human tissues, showed that in addition to HOXA10, also HOXA9, HOXA11, HOXB6 and HOXD10 mRNA showed increased expression in the human endometrium (16 samples). The temporal and spatial expression pattern of these four HOX genes throughout the menstrual cycle was determined in the endometrium from 27 female patients eligible for IVF-embryo transfer with a normal cycle by quantitative real-time PCR (qRT-PCR), western blot and immunohistochemistry. The role of maternal Hoxa9, Hoxa11 and Hoxd10 was assessed in a mouse implantation model by expression knockdown using RNA interference. Forty mice were transfected with Hoxa9-, Hoxa11- or Hoxd10-specific small hairpin RNA (shRNA) constructs or a vector control by injection into the uterine horn at Day 2 after vaginal plug detection (Day 1) (160 mice in total). The effects were examined by qRT-PCR and western blot at Day 4 and litter sizes counted at Day 9 of pregnancy. HOXA10, HOXA9, HOXA11 and HOXD10 all showed increased expression during the mid-secretory phase of the menstrual cycle (P < 0.01). Knockdown of Hoxa9, Hoxa11 and Hoxd10 in the murine uterus resulted in significantly reduced average implantation rates (P < 0.01) and, with regard to four Hox target genes, also correlated with a significantly increased empty spiracles homolog 2 (Emx2) and insulin-like growth factor binding protein-1 (Igfbp1), and decreased integrin β3 (Itgb3) and leukemia inhibitory factor (Lif), expression (P < 0.01). Menstrual cycle stage was not confirmed by serum hormone analysis. We verified the absence of significant differences in stage-specific expression of the reference genes used in our study (ACTB/Actb and GAPDH/Gapdh) and therefore possible limitations of this approach were minimized. In addition, the translatability of our data from a mouse model to patients needs to be investigated further. We provide evidence that three other HOX genes in addition to HOXA10 are involved in endometrial receptivity, and that part of their function is asserted through several known HOX target genes, suggesting the presence of a central HOX signal transduction pathway.

Multiple regulatory safeguards confine the expression of the GATA factor Serpent to the hemocyte primordium within the Drosophila mesoderm

serpent (srp) encodes a GATA-factor that controls various aspects of embryogenesis in Drosophila, such as fatbody development, gut differentiation and hematopoiesis. During hematopoiesis, srp expression is required in the embryonic head mesoderm and the larval lymph gland, the two known hematopoietic tissues of Drosophila, to obtain mature hemocytes. srp expression in the hemocyte primordium is known to depend on snail and buttonhead, but the regulatory complexity that defines the primordium has not been addressed yet. Here, we find that srp is sufficient to transform trunk mesoderm into hemocytes. We identify two disjoint cis-regulatory modules that direct the early expression in the hemocyte primordium and the late expression in mature hemocytes and lymph gland, respectively. During embryonic hematopoiesis, a combination of snail, buttonhead, empty spiracles and even-skipped confines the mesodermal srp expression to the head region. This restriction to the head mesoderm is crucial as ectopic srp in mesodermal precursors interferes with the development of mesodermal derivates and promotes hemocytes and fatbody development. Thus, several genes work in a combined fashion to restrain early srp expression to the head mesoderm in order to prevent expansion of the hemocyte primordium.

Nav1.1 haploinsufficiency in excitatory neurons ameliorates seizure-associated sudden death in a mouse model of Dravet syndrome

Dravet syndrome is a severe epileptic encephalopathy mainly caused by heterozygous mutations in the SCN1A gene encoding a voltage-gated sodium channel Nav1.1. We previously reported dense localization of Nav1.1 in parvalbumin (PV)-positive inhibitory interneurons in mice and abnormal firing of those neurons in Nav1.1-deficient mice. In the present study, we investigated the physiologic consequence of selective Nav1.1 deletion in mouse global inhibitory neurons, forebrain excitatory neurons or PV cells, using vesicular GABA transporter (VGAT)-Cre, empty spiracles homolog 1 (Emx1)-Cre or PV-Cre recombinase drivers. We show that selective Nav1.1 deletion using VGAT-Cre causes epileptic seizures and premature death that are unexpectedly more severe than those observed in constitutive Nav1.1-deficient mice. Nav1.1 deletion using Emx1-Cre does not cause any noticeable abnormalities in mice; however, the severe lethality observed with VGAT-Cre-driven Nav1.1 deletion is rescued by additional Nav1.1 deletion using Emx1-Cre. In addition to predominant expression in PV interneurons, we detected Nav1.1 in subpopulations of excitatory neurons, including entorhino-hippocampal projection neurons, a subpopulation of neocortical layer V excitatory neurons, and thalamo-cortical projection neurons. We further show that even minimal selective Nav1.1 deletion, using PV-Cre, is sufficient to cause spontaneous epileptic seizures and ataxia in mice. Overall, our results indicate that functional impairment of PV inhibitory neurons with Nav1.1 haploinsufficiency contributes to the epileptic pathology of Dravet syndrome, and show for the first time that Nav1.1 haploinsufficiency in excitatory neurons has an ameliorating effect on the pathology.

EMX2 is Downregulated in Endometrial Cancer and Correlated With Tumor Progression

EMX2 (the human homologue of Drosophila empty spiracles gene 2) is a candidate tumor suppressor. However, its roles in endometrial cancer are still unknown. In this study, we evaluated EMX2 expression in different subtypes of endometrial cancer and its relationships with clinicopathologic characteristics. By immunohistochemical staining, we investigated the level of EMX2 protein in 122 endometrial cancer and 25 normal endometrium tissues. Correlations between EMX2 expression and clinicopathologic features of patients were analyzed using a statistical software. Compared with the normal endometrium, the expression of EMX2 was significantly downregulated in endometrial cancer tissues (P< 0.001). Reduced EMX2 expression was correlated with the tumor stage (P = 0.023), grade (P = 0.016), and the depth of myometrial invasion (P = 0.04), but not with age, pathologic subtype, lymph node metastasis, lymph vascular space invasion, or ER/PR/p53 status. Downregulation of EMX2 was associated with tumor progression and may be a critical factor in the carcinogenesis and progression of endometrial cancer, which provided a novel therapeutic target and a potential marker for prognostic prediction.

Antagonism Versus Cooperativity with TALE Cofactors at the Base of the Functional Diversification of Hox Protein Function

Extradenticle (Exd) and Homothorax (Hth) function as positive transcriptional cofactors of Hox proteins, helping them to bind specifically their direct targets. The posterior Hox protein Abdominal-B (Abd-B) does not require Exd/Hth to bind DNA; and, during embryogenesis, Abd-B represses hth and exd transcription. Here we show that this repression is necessary for Abd-B function, as maintained Exd/Hth expression results in transformations similar to those observed in loss-of-function Abd-B mutants. We characterize the cis regulatory module directly regulated by Abd-B in the empty spiracles gene and show that the Exd/Hth complex interferes with Abd-B binding to this enhancer. Our results suggest that this novel Exd/Hth function does not require the complex to bind DNA and may be mediated by direct Exd/Hth binding to the Abd-B homeodomain. Thus, in some instances, the main positive cofactor complex for anterior Hox proteins can act as a negative factor for the posterior Hox protein Abd-B. This antagonistic interaction uncovers an alternative way in which MEIS and PBC cofactors can modulate Abd-B like posterior Hox genes during development.

Zebrafish dmrta2 Regulates the Expression of cdkn2c in Spermatogenesis in the Adult Testis1

The exact function of the doublesex and mab-3 related transcription factor-like family a2 gene (dmrta2) has remained largely unknown possibly because of its functional redundancy with dmrta1 in most vertebrates. In this study, dmrta1 was demonstrated to likely be absent in the zebrafish genome, which facilitated our functional analysis of dmrta2 in this model organism. To analyze its gene function in embryos and adults, we generated a mutant form of Dmrta2 (R106Q, Dmrta2(RQ)) with its in vitro DNA-binding capacity abolished and a transgenic line for the inducible expression of this mutant Dmrta2(RQ) upon doxycycline (Dox) treatment. Preferential dmrta2 expression was detected in the developing brain during embryogenesis and in the adult testis. During embryogenesis, Dmrta2(RQ) expression caused severe embryonic development defects and dramatic expression changes of two telencephalic marker genes, fibroblast growth factor 8a (fgf8a), and empty spiracles homolog 1 (emx1). In adults, the inducible Dmrta2(RQ) expression occurred specifically in the adult testis and recapitulated the endogenous dmrta2 expression in this organ. Intriguingly, adult males expressing dmrta2(RQ) showed normal spermatogenesis and were fertile, but the expression of cyclin-dependent kinase inhibitor 2C (cdkn2c), which is evolutionarily clustered with dmrta2, was significantly suppressed during spermatogenesis. Further protein-binding and promoter mutation analysis indicated that a putative Dmrta2-binding site on the cdkn2c promoter was required for sustaining the normal expression of cdkn2c during zebrafish spermatogenesis, suggesting that Dmrta2 might regulate the expression of cdkn2c.

Adenoviral Delivery of the EMX2 Gene Suppresses Growth in Human Gastric Cancer

BackgroundEMX2 is a human orthologue of the Drosophila empty spiracles homeobox gene that has been implicated in embryogenesis. Recent studies suggest possible involvement of EMX2 in human cancers; however, the role of EMX2 in carcinogenesis needs further exploration.ResultsIn this study, we reported that down-regulation of EMX2 expression was significantly correlated with EMX2 promoter hypermethylation in gastric cancer. Restoring EMX2 expression using an adenovirus delivery system in gastric cancer cell lines lacking endogenous EMX2 expression led to inhibition of cell proliferation and Wnt signaling pathway both in vitro and in a gastric cancer xenograft model in vivo. In addition, we observed that animals treated with the adenoviral EMX2 expression vector had significantly better survival than those treated with empty adenoviral vector.ConclusionOur study suggests that EMX2 is a putative tumor suppressor in human gastric cancer. The adenoviral-EMX2 may have potential as a novel gene therapy for the treatment of patients with gastric cancer.