We used microarrays to determine the effect of prenatal nicotine exposure on gene expression profiles in the striatum of adolescent rats. We found a number of immediate early genes to be differentially expressed due to food-restriction.
Long-term effects of gestational nicotine exposure and food-restriction on gene expression in the striatum of adolescent rats.
Specimen part
View SamplesWnt signaling in early eye development, specifically the lens placode shows expression of 12 out of 19 Wnt ligands. We these Wnt activities were suppressed using conditional deletion of Wntless, dramatic phenotypic changes in morphogensis occurred.
Wnt ligands from the embryonic surface ectoderm regulate 'bimetallic strip' optic cup morphogenesis in mouse.
Specimen part
View SamplesThe coupling between cell-cycle exit and onset of differentiation is a common feature throughout the developing nervous system, but the mechanisms that link these processes are mostly unknown. Although the transcription factor Pax6 was implicated in both proliferation and differentiation of multiple regions within the CNS, its contribution to the transition between these successive states remains elusive. To gain insight into the role of Pax6 during the transition from proliferating progenitors to differentiating precursors, we investigated cell-cycle and transcriptomic changes occurring in Pax6- retinal progenitor cells (RPCs). Our analyses revealed a unique cell-cycle phenotype of the Pax6-deficient RPCs, which included a reduced number of cells in the S phase, an increased number of cells exiting the cell cycle, and delayed differentiation kinetics of Pax6- precursors. These alterations were accompanied by co-expression of factors that promote (Ccnd1, Ccnd2, Ccnd3) and inhibit (P27kip1 and P27kip2) the cell cycle. Further characterization of the changes in transcription profile of the Pax6-deficient RPCs revealed abrogated expression of multiple factors which are known to be involved in regulating proliferation of RPCs, including the transcription factors Vsx2, Nr2e1, Plagl1 and Hedgehog signaling. These findings provide novel insight into the molecular mechanism mediating the pleiotropic activity of Pax6 in RPCs. The results further suggest that rather than conveying a linear effect on RPCs, such as promoting their proliferation and inhibiting their differentiation, Pax6 regulates multiple transcriptional networks which function simultaneously, thereby conferring the capacity to proliferate, assume multiple cell fates and execute the differentiation program into retinal lineages.
Pax6 is required for normal cell-cycle exit and the differentiation kinetics of retinal progenitor cells.
Specimen part
View SamplesSingle-neuron transcriptome profiles of Dorsal Raphe neurons marked by a history of expression of Drd2::Cre and Pet1::Flpe (GFP+), as well as Dorsal Raphe neurons marked by a history of Pet1::Flpe expression only (mCherry+). Overall design: GFP and mCherry expressing neurons from triple transgenic Drd2::Cre;Pet1::Flpe;RC:FrePe mice were acutely dissociated, manually sorted, and single-neuron RNA-seq was performed (17 GFP+ cells, 8 mCherry+ cells).
Identification of Serotonergic Neuronal Modules that Affect Aggressive Behavior.
Specimen part, Subject
View SamplesPhysical performance relies on the concerted action of myriad responses, many of which are under circadian clock control. Little is known, however, regarding the time-dependent effect on exercise performance at the molecular level. We found that both mice and humans exhibit day-time variance in exercise capacity between the early and late part of their active phase. The day-time variance in mice was dependent on exercise intensity and relied on the circadian clock proteins PER1/2. High throughput gene expression and metabolic profiling of skeletal muscle revealed metabolic pathways that are differently activated upon exercise in a day-time dependent manner. Remarkably, we discovered that ZMP, an endogenous AMPK activator, is induced by exercise in a time-dependent manner to regulate key steps in glycolytic and fatty acid oxidation pathways and potentially enhance exercise capacity. Overall, we propose that time of the day is a major modifier of exercise capacity and associated metabolic pathways. Overall design: basal, high intensity and moderate intensity runnig protocol at ZT14 and ZT22 in gastrocnemius muscle in C57B6 mice
Physiological and Molecular Dissection of Daily Variance in Exercise Capacity.
Sex, Cell line, Subject, Time
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MicroRNAs are essential for differentiation of the retinal pigmented epithelium and maturation of adjacent photoreceptors.
Specimen part, Treatment
View SamplesDysfunction of the retinal pigmented epithelium (RPE) results in degeneration of photoreceptors and vision loss and is correlated with common blinding disorders in humans. Although many protein-coding genes are known to be expressed in RPEs and important for their development and maintenance, virtually nothing is known about the in vivo roles of non-protein coding transcripts in RPEs. The expression patterns of microRNAs (miRNAs) have been analyzed in a variety of ocular tissues, and few were implicated to play role in RPE based on studies in cell lines. Herein, through RPE specific conditional mutagenesis of Dicer1 or DGCR8, the importance of miRNA for RPE differentiation was uncovered. Interestingly, miRNAs were found to be dispensable for maintaining the RPE fate and survival, and yet they are essential for acquisition of important RPE properties such as the expression of genes involved in the visual cycle pathway, pigmentation and cell adhesion. Importantly miRNAs of the RPE were found to be required for maturation of the adjacent photoreceptors, specifically for the morphogenesis of the outer segments. The profiles of miRNA and mRNA altered in the Dicer1 deficient RPE point to a key role of miR-204 in regulation of RPE differentiation program in vivo and uncovers the importance of additional novel RPE miRNAs. The study exposes the combined regulatory activity of miRNAs of the RPE, which is required for RPE differentiation and for the development of the adjacent neuroretina.
MicroRNAs are essential for differentiation of the retinal pigmented epithelium and maturation of adjacent photoreceptors.
Specimen part, Treatment
View SamplesThis is a comparative microarray analysis of LE-AP-2a mutants vs. wild-type P0 littermate lenses.
Cell autonomous roles for AP-2alpha in lens vesicle separation and maintenance of the lens epithelial cell phenotype.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Competition between virus-derived and endogenous small RNAs regulates gene expression in Caenorhabditis elegans.
No sample metadata fields
View SamplesAnalysis of the transcriptional response to viral infection in C.elegans.
Competition between virus-derived and endogenous small RNAs regulates gene expression in Caenorhabditis elegans.
No sample metadata fields
View Samples