We found that the previously published Fmr1 knockout rat model of FXS expresses an Fmr1 transcript with an in-frame deletion of exon 8, which encodes for the K-homology (KH) RNA-binding domain, KH1. We observed that the deletion of exon 8 in 10 male rats within the medial prefrontal cortex (mPFC) led to transcriptional alterations compared to 12 WT rats using RNAseq. Additionally, we used weighted gene co-expression network analysis to generate 23 modules specific to the mPFC with tissue from 35 WT rat samples. Overall design: RNAseq using WT and Fmr1 delta exon 8 mPFC samples
Deletion of the KH1 Domain of Fmr1 Leads to Transcriptional Alterations and Attentional Deficits in Rats.
Age, Specimen part, Cell line, Subject
View SamplesWe generated whole genome expression profiles from a homogeneous population of purified pacemaker neurons (ventral Lateral Neurons, LNvs) from wild type and clock mutant Drosophila. The study identifes a group of genes whose expression is highly enriched in LNvs compared to other neurons; and a second group of genes rhythmically expressed in LNvs in a clock-dependent manner.
A mechanism for circadian control of pacemaker neuron excitability.
Specimen part
View SamplesSeveral transcription factors are known to be expressed in discrete regions of the otic vesicle and Dlx5 is one of those that is expressed highly in the presumptive dorsal vestibular region. Mice lacking Dlx5 have vestibular defects. Specifically, they fail to form the endolymphatic duct (a defect visible as early as E10) as well as the anterior and posterior semi-circular canals. The lateral canal does form but is smaller, whereas the saccule, the utricle and the cochlea appear relatively normal. The goal of this study was to use microarrays to identify differentially expressed genes between wild-type and Dlx5-null otic vesicles microdissected from E10 and 10.5 and identify downstream targets of Dlx5 by searching the immediate 3kb promoter regions of the differentially expressed genes for homeodomain binding sites followed by chromatin immunoprecipitation in an otic vesicle-derived cell line over-expressing Dlx5.
Identification of direct downstream targets of Dlx5 during early inner ear development.
Age, Specimen part
View SamplesDeprivation of peripheral nerve input by cochlear removal in young mice results in dramatic neuron death in the cochlear nucleus (CN). The same manipulation in older mice does not result in significant loss. The molecular basis of this critical period of vulnerability remains largely unknown. Here we identified genes regulated at early time points after cochlear removal at ages when neurons are vulnerable (postnatal day (P)7) or invulnerable (P21) to this challenge. Afferent deprivation regulated very different sets of genes at P7 and P21. These genes showed a variety of functions at both ages, but surprisingly there was no net increase in pro-apoptotic genes at P7. A large set of upregulated immune-related genes was identified at P21.
Afferent deprivation elicits a transcriptional response associated with neuronal survival after a critical period in the mouse cochlear nucleus.
No sample metadata fields
View SamplesThe Dlx homeobox genes have central roles in controlling patterning and differentiation of the brain and craniofacial primordia. In the brain, loss of Dlx function results in defects in the production, migration and differentiation of GABAergic neurons, that can lead to epilepsy. In the branchial arches, loss of Dlx function leads to craniofacial malformations that include trigeminal axon pathfinding defects. To determine how these genes function, we wish to identify the transcriptional circuitry that lies downstream of these transcription factors by comparing gene expression in wild type with Dlx mutant CNS and craniofacial tissues.
Dlx genes pattern mammalian jaw primordium by regulating both lower jaw-specific and upper jaw-specific genetic programs.
No sample metadata fields
View SamplesWe analyzed whether cochlear removal-induced transcriptional changes in the cochlear nucleus (CN) were due to loss of electrical activity in the 8th nerve. Pharmacological activity blockade of the auditory nerve for 24 h resulted in similar expression changes for only a subset of genes. Thus, an additional factor not dependent on action potential-mediated signaling must also regulate transcriptional responses to deafferentation in the CN.
Afferent deprivation elicits a transcriptional response associated with neuronal survival after a critical period in the mouse cochlear nucleus.
No sample metadata fields
View SamplesOverview: We report here that gene expression in E13.5 wild type (WT) mouse lenses differs from the lenses of mice that conditionally lack the Prox1 transcription factor in the lens of their eyes (Prox1 cKO) as assayed by high throughput RNA sequencing (RNAseq). The methodology outlined herein is similar to a previous RNAseq experiment from our lab (Manthey et al., 2014a)(Geo ascension: GSE 49949), and the filtering and processing criteria for this experiment was published as well.(Manthey et al., 2014b). The mammalian lens is notable for its biased gene expression, where 90% of the observed protein is expressed by just 50 genes. RNAseq was employed to sequence past these highly expressed lens structural genes and report the relative abundance of both high and low expression genes. In this study we demonstrated that 642 genes were differentially expressed in the lenses of Prox1 cKOs as compared to WT lenses. These data were analyzed using the DAVID biostatical analysis package and we found that the expression of lens specific proteins, as well as cytoskeletal genes and genes that regulated the cytoskeleton were expressed at lower levels in Prox1 cKOs. This analysis showed that the expression of genes encoding extracellular matrix components and their regulators, as well as cell adhesion increased in Prox1 cKO lenses when compared to WTs. Description of Filtering Criteria: Our initial analysis identified 5,492 genes that were differentially expressed in Prox1 cKO lenses as compared to WTs as computed by Pair-wise qCML method exact tests with a Benjamini Hochberg false discovery rate correction greater than the threshold of P < 0.05. As we described previously, there is significant variation in gene expression between inbred C57Bl/6 <har> and mice with a mixed background below a threshold of 2.5 fold. For this reason we filtered out all genes whose differential expression was less than 2.5 fold. We also wanted to filter out genes that were expressed at such low levels that they were unlikely to impact cellular function. We restricted our list to those genes that were expressed at greater than 2 Reads per Kilobase per million reads (RPKM) in either WT or Prox1 cKO samples, a value which corresponds to approximately 1 mRNA molecule per cell. The application of these filtering criteria resulted in narrowing our list to 642 genes that were likely to impact the Prox1 cKO lens phenotype. Manthey, A. L., Lachke, S. A., FitzGerald, P. G., Mason, R. W., Scheiblin, D. A., McDonald, J. H. and Duncan, M. K. (2014a) ''Loss of Sip1 leads to migration defects and retention of ectodermal markers during lens development'', Mech Dev 131: 86-110. Manthey, A. L., Terrell, A. M., Lachke, S. A., Polson, S. W. and Duncan, M. K. (2014b) ''Development of novel filtering criteria to analyze RNA-sequencing data obtained from the murine ocular lens during embryogenesis'', Genom Data 2: 369-374. Overall design: RNA-Seq comparison of C57Bl/6 <har> wild type controls and Prox1 conditional knockout lenses at E13.5
Prox1 and fibroblast growth factor receptors form a novel regulatory loop controlling lens fiber differentiation and gene expression.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Research resource: Genome-wide profiling of progesterone receptor binding in the mouse uterus.
Sex, Age, Specimen part, Treatment
View SamplesProgesterone (P4) signaling through its nuclear transcription factor, the progesterone receptor (PR), is essential for normal uterine function. Although deregulation of PR mediated signaling is known to underscore uterine dysfunction and a number of endometrial pathologies, the early molecular mechanisms of this deregulation are unclear. To address this issue, we have defined the genome-wide PR and GATA2 cistrome in the murine uterus using chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-seq). In uteri of ovariectomized mice, we identified 6367 PR binding sites in the absence of P4 ligand; however, this number increased at nearly three fold (18,432) following acute P4 exposure. Sequence analysis revealed that approximately 73% of these binding sites contain a progesterone response element (PRE) or a half-site motif recognized by the PR. Many previously identified P4 target genes known to regulate uterine function were found to contain PR binding sites, confirming the validity of our methodology. In addition we identified 46,183 GATA2 binding sites in P4 treatment conditions with 7,954 binding sites overlapping that of the PR.
Research resource: Genome-wide profiling of progesterone receptor binding in the mouse uterus.
Sex, Age, Specimen part
View SamplesSingle-cell RNA-Seq RNA from medial ganglionic eminence at E11.5, E13.5, E15.5 or E17.5. The ID of this project in Genentech''s ExpressionPlot database is PRJ0007389 Overall design: Single-cell RNA-Seq from medial ganglionic eminence at E11.5, E13.5, E15.5 or E17.5.
Single-cell RNA sequencing identifies distinct mouse medial ganglionic eminence cell types.
Specimen part, Subject
View Samples