One of the central issues in evolutionary developmental biology is how we can formulate the relationships between evolutionary and developmental processes. Two major models have been proposed: the 'funnel-like' model, in which the earliest embryo shows the most conserved morphological pattern, followed by diversifying later stages, and the 'hourglass' model, in which constraints are imposed to conserve organogenesis stages, which is called the phylotypic period. Here we perform a quantitative comparative transcriptome analysis of several model vertebrate embryos and show that the pharyngula stage is most conserved, whereas earlier and later stages are rather divergent. These results allow us to predict approximate developmental timetables between different species, and indicate that pharyngula embryos have the most conserved gene expression profiles, which may be the source of the basic body plan of vertebrates.
Comparative transcriptome analysis reveals vertebrate phylotypic period during organogenesis.
Sex, Specimen part, Disease, Disease stage
View SamplesTranscription profiling of mouse development
Comparative transcriptome analysis reveals vertebrate phylotypic period during organogenesis.
Sex, Specimen part, Disease, Disease stage
View SamplesThere is evidence for the beneficial effect of FK506, an effective immunosuppressive agent, for the treatment of asthma however, the mechanisms underlying these effects are unclear. Using a mouse model of airway inflammation induced by Papain, a protease allergen, and RNAseq analysis of lung innate cells, we found that FK506 inhibited the activation of ILC2s, which initiate airway inflammation, as well as the induction of TH2 cells, which cause chronic inflammation. Our findings further support the clinical value of FK506 for the treatment of allergen-induced airway inflammation and clarify its targets and mechanisms of action. Overall design: Lung ILC2 cells, epithlial cells (type 1: AEC1 and type 2: AEC2), and basophils of mice were sorted and analyzed the transcriptome using Illumina HiSeq1500.
No associated publication
Age, Specimen part, Genotype, Treatment, Subject
View SamplesThe innate immune system is a two-edged sword; it is absolutely required for host defense against infection, but if left uncontrolled can trigger a plethora of inflammatory diseases. Here we used systems biology approaches to predict and validate a gene regulatory network involving a dynamic interplay between the transcription factors NF-B, C/EBP, and ATF3 that controls inflammatory responses. We mathematically modeled transcriptional regulation of Il6 and Cebpd genes and experimentally validated the prediction that the combination of an initiator (NF-B), an amplifier (C/EBP) and an attenuator (ATF3) forms a regulatory circuit that discriminates between transient and persistent Toll-like receptor 4-induced signals. Our results suggest a mechanism that enables the innate immune system to detect the duration of infection and to respond appropriately.
Function of C/EBPdelta in a regulatory circuit that discriminates between transient and persistent TLR4-induced signals.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Evolutionary etiology of high-grade astrocytomas.
Sex, Time
View SamplesTo determine the regulatory pathways necessary for astrocytoma formation within complex adult brain microenvironments, we engineered mice for adult astrocyte-specific disruption of key regulators (pRb, Kras and Pten). Drivers of all astrocytoma grades were identified using CreERTM-inducible alleles. Inactivation of pRb was necessary to initiate grade II disease, and was the only lesion to do so. Additional activation of Kras progressed disease to grade III, while further Pten inactivation facilitated grade IV (glioblastoma) progression. These outcomes were elicited whether somatic events were induced broadly or focally. In vivo inactivation of pRb, which induced astrocyte proliferation and apoptosis, activated the MAPK pathway, while Kras activation and Pten loss triggered PI3K pathways.
Evolutionary etiology of high-grade astrocytomas.
Sex, Time
View SamplesThe adult mammalian brain is composed of distinct regions that have specialized roles. The BF/POA regions are thought to have an important role in the regulation of sleep/wake behavior. However, genetic markers of the responsible cells for the regulation of sleep/wake behavior are largely unknown. To identify the molecular markers of the BF/POA regions, we sampled the BF/POA regions and compared gene expression in the BF/POA regions with those of other brain regions which we previously reported in the BrainStars (B*) project, in which we sampled ~50 small brain regions, including sensory centers and centers for motion, time, memory, fear, and feeding.
Muscarinic Acetylcholine Receptors Chrm1 and Chrm3 Are Essential for REM Sleep.
Sex, Specimen part
View SamplesThe adult mammalian brain is composed of distinct regions that have specialized roles. To dissect molecularly this complex structure, we conducted a project, named the BrainStars (B*) project, in which we sampled ~50 small brain regions, including sensory centers and centers for motion, time, memory, fear, and feeding. To avoid confusion from temporal differences in gene expression, we sampled each region every 4 hours for 24 hours, and pooled the sample sets for DNA-microarray assays. Therefore, we focused only on spatial differences in gene expression. We then used informatics to identify candidates for (1) genes with high or low expression in specific regions, (2) switch-like genes with bimodal or multimodal expression patterns, and (3) genes with a uni-modal expression pattern that exhibit stable or variable levels of expression across brain regions. We used our findings to develop an integrated database (http://brainstars.org/) for exploring genome-wide expression in the adult mouse brain.
Quantitative expression profile of distinct functional regions in the adult mouse brain.
Sex, Specimen part
View SamplesCellular diversity of the brain is largely attributed to the spatial and temporal heterogeneity of progenitor cells. In mammalian cerebral development, it has been difficult to determine how neural progenitor cells are heterogeneous, due to their dynamic changes in nuclear position and gene expression. To address this issue, we systematically analyzed the cDNA profiles of a large number of single progenitor cells at the mid-embryonic stage.
No associated publication
Specimen part
View SamplesLiving organisms detect seasonal changes in day length (photoperiod), and alter their physiological functions accordingly, to fit seasonal environmental changes. This photoperiodic system is implicated in seasonal affective disorders and the season-associated symptoms observed in bipolar disease and schizophrenia. Thyroid-stimulating hormone beta subunit (Tshb), induced in the pars tuberalis (PT), plays a key role in the pathway that regulates animal photoperiodism. However, the upstream inducers of Tshb expression remain unknown. Here we show that late-night light stimulation acutely triggers the Eya3-Six1 pathway, which directly induces Tshb expression. Using melatonin-proficient CBA/N mice, which preserve the photoperiodic Tshb-expression response, we performed a genome-wide expression analysis of the PT under chronic short-day and long-day conditions. These data comprehensively identified long-day and short-day genes, and indicated that late-night light stimulation induces long-day genes. We verified this by advancing and extending the light period by 8 hours, which acutely induced Tshb expression, within one day. In a genome-wide expression analysis under this condition, we searched for candidate upstream genes by looking for expression that preceded Tshbs, and identified Eya3 gene. These results elucidate the comprehensive transcriptional photoperiodic response in the PT, revealing the complex regulation of Tshb expression and unexpectedly rapid response to light changes in the mammalian photoperiodic system.
Acute induction of Eya3 by late-night light stimulation triggers TSHβ expression in photoperiodism.
Sex, Age, Specimen part, Time
View Samples