We have demonstrated previously that mammalian sexual differentiation requires both GATA4 and FOG2 transcription regulators to assemble the functioning testis. We have now determined that the sexual development of female mice is profoundly affected by the loss of GATA4-FOG2 interaction. We have also identified the Dkk1 gene, encoding a secreted inhibitor of canonical -catenin signaling as a target of GATA4/FOG2 repression in the developing ovary. The tissue-specific ablation of the -catenin gene in the gonads disrupts female development while in the Gata4ki/ki/Dkk1-/- or Fog2-/-/Dkk1-/- embryos the normal ovarian gene expression pattern is partially restored. Control of ovarian development by the GATA4/FOG2 complex presents a novel insight into the crosstalk of transcriptional regulation and extracellular signaling in ovarian development.
Ovarian development in mice requires the GATA4-FOG2 transcription complex.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The epigenetic processes of meiosis in male mice are broadly affected by the widely used herbicide atrazine.
Specimen part
View SamplesEnvironmental factors such as pesticides are widely used in the agriculture of many countries and their negative impact on human health and fertility are largely unknown. There is a rapidly growing body of evidence that human reproductive health is negatively affected by the various environmental factors, including life style and exposure to the chemical compounds such as certain drugs and pesticides. Sexually reproducing organisms produce haploid gametes via a process called meiosis. Meiosis is dependent on androgen action within the testis. Pesticides and herbicides interfere with natural hormones system and are considered to be endocrine disruptors. We hypothesize that atrazine (ATZ), a herbicide used globally, adversely affects meiosis. To test this idea we used the mouse as a model organism. Mice were treated three weeks with atrazine in drinking water at concentration of 100 mg/l. To assess the molecular mechanisms of effects of ATZ on spermatogenesis we performed comparative analysis of genes expression by using Affymetrix microarray by using three biological testis samples from ATZ treated and control mice. Using a fold-change cutoff value of 1.5 and p value <0.05 (statistical Limma test (linear models test for microarray data)), we identified 51 genes that were differentially expressed in ATZ treated mice.
The epigenetic processes of meiosis in male mice are broadly affected by the widely used herbicide atrazine.
Specimen part
View SamplesThe DNA-binding protein, Ikaros, functions as a potent tumor suppressor and hematopoietic regulator. However, the mechanisms by which Ikaros functions in the nucleus remain largely undefined, due in part to its atypical DNA-binding properties and partnership with the poorly understood Mi-2/NuRD complex. In this study, we extended our analysis of thymocyte development and lymphomagenesis in a mouse strain containing a specific deletion of Ikaros zinc finger 4, which exhibits a select subset of abnormalities observed in Ikaros null mice. By examining thymopoiesis in vivo and in vitro, numerous abnormalities were observed. RNA-sequencing revealed that each developmental stage is characterized by mis-regulation of a limited number of genes, with a strong preference for genes modulated in a stage-specific manner. Strikingly, individual genes and pathways rarely exhibited Ikaros-dependence at all developmental stages. Instead, the most consistent feature of aberrantly expressed genes was a reduced magnitude of expression level change during a developmental transition. These results and others suggest that Ikaros may not be a dedicated and consistent activator or repressor of a defined set of genes. Instead, its primary function may be to support the dynamic range of gene expression changes during developmental transitions via atypical molecular mechanisms that remain undefined. Overall design: RNA-Seq of T cells at varying developmental stages and T cells expressing activated Notch in WT and Ikzf1-dF4/dF4 mutant backgrounds
Regulation of gene expression dynamics during developmental transitions by the Ikaros transcription factor.
No sample metadata fields
View SamplesThe role of estrogen and testosterone in the regulation of gene expression in the proximal reproductive tract is not completely understood. To address this question, mice were treated with testosterone or estradiol and RNA from the efferent ducts and caput epididymis was processed and hybridized to Affymetrix MOE 430 2.0 microarrays. Analysis of array output identified probe sets in each tissue with altered levels in hormone treated versus control animals. Hormone treatment efficacy was confirmed by determination of serum hormone levels pre- and post-treatment and observed changes in transcript levels of previously reported hormone-responsive genes. Tissue-specific hormone sensitivity was observed with 2867 and 3197 probe sets changing significantly in the efferent ducts after estrogen and testosterone treatment, respectively. In the caput epididymis, 117 and 268 probe sets changed after estrogen and testosterone treatment, respectively, demonstrating a greater response to hormone in the efferent ducts than the caput epididymis. Transcripts sharing similar profiles in the intact and hormone-treated animals compared with castrated controls were also identified. Ontological analysis of probe sets revealed a significant number of hormone-regulated transcripts encode proteins associated with lipid metabolism, transcription and steroid metabolism in both tissues. Real-time RT-PCR was employed to confirm array data and investigate other potential hormone-responsive regulators of proximal reproductive tract function. The results of this work reveal previously unknown responses to estrogen in the caput epididymis and to testosterone in the efferent ducts as well as tissue specific hormone sensitivity in the proximal reproductive tract.
Regulation of gene expression by estrogen and testosterone in the proximal mouse reproductive tract.
Sex, Specimen part, Treatment
View SamplesA microarray study of sex- and gonad-biased gene expression was conducted to determine whether zebrafish demonstrate male-specific patterns consistent with those observed in other animals. We identified a large number of genes (5899) demonstrating statistical differences in transcript abundance between male and female Danio rerio. All sex-biases in gene expression were due to differences between testis and ovary, although differences between male and female body likely went undetected due to constraints imposed by study design and statistical criteria. Male-enriched genes were more abundant than female-enriched genes, and the magnitude of expression bias for male-enriched genes was greater than that for female-enriched genes. We also identified a large number of candidate reproductive genes based on elevated transcript abundance in testes and ovaries, relative to male body and female body, respectively. Gene expression patterns in adult zebrafish from this study are consistent with the male-biased patterns typical of most animal taxa studied to date. Recent zebrafish studies designed to address more specific questions have not reported the same findings, but major methodological and analytical differences across these studies could explain discrepancies.
A microarray analysis of sex- and gonad-biased gene expression in the zebrafish: evidence for masculinization of the transcriptome.
Sex
View SamplesEndothelin signaling is required for neural crest migration and homeostatic regulation of blood pressure. Here we report that constitutive over-expression of Endothelin-2 (Edn2) in the mouse retina perturbs vascular development by inhibiting endothelial cell (EC) migration across the retinal surface and subsequent EC invasion into the retina. Developing endothelial cells exist in one of two states: tip cells at the growing front, and stalk cells in the vascular plexus behind the front. This division of endothelial cell states is one of the central organizing principle of angiogenesis. In the developing retina, Edn2 over-expression leads to over-production of endothelial tip cells by both morphologic and molecular criteria. Spatially localized over-expression of Edn2 produces a correspondingly localized endothelial response. Edn2 over-expression in the early embryo inhibits vascular development at mid-gestation, but Edn2 over-expression in developing skin and brain has no discernable effect on vascular structure. Inhibition of retinal angiogenesis by Edn2 requires expression of Endothelin receptor A (Ednra) but not Ednrb in the neural retina. Taken together, these observations imply that the neural retina responds to Edn2 by synthesizing one or more factors that promote the endothelial tip cell state and inhibit angiogenesis. The response to Edn2 is sufficiently potent that it over-rides the activities of other homeostatic regulators of angiogenesis, such as vascular endothelial growth factor.
Endothelin-2 signaling in the neural retina promotes the endothelial tip cell state and inhibits angiogenesis.
Specimen part
View SamplesWe used arrays to examine the overall transcriptional differences between WT K-12 E. coli, and EHEC 86-24 and their corresponding QseD (yjiE) mutants.
The LysR-type transcriptional regulator QseD alters type three secretion in enterohemorrhagic Escherichia coli and motility in K-12 Escherichia coli.
No sample metadata fields
View SamplesWe developed a Tet-inducible system to express deltaNp63alpha isoform under the control of keratin 5 promoter. Transgenic mice, which were Bigenic (BG) developed a severe skin phenotype with abnormal keratinocyte differentiation and defects in hair follicle development and cycling. Skin samples from transgenic animals and wild type animals were analyzed for global transcriptome changes.
Abnormal hair follicle development and altered cell fate of follicular keratinocytes in transgenic mice expressing DeltaNp63alpha.
Specimen part
View SamplesTime course of gene expression in the murine embryonic testis from the time of the indifferent gonad (11.5dpc) to birth (18.5dpc)
Profiling gene expression during the differentiation and development of the murine embryonic gonad.
No sample metadata fields
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