Alpha-synuclein is an abundant protein implicated in synaptic function and plasticity, but the molecular mechanism of its action is not understood. Missense mutations and gene duplication/triplication events result in Parkinson's disease, a neurodegenerative disorder of old age with impaired movement and emotion control. Here, we systematically investigated the striatal as well as the cerebellar transcriptome profile of alpha-synuclein-deficient mice via a genome-wide microarray survey in order to gain hypothesis-free molecular insights into the physiological function of alpha-synuclein. A genotype-dependent, specific and strong downregulation of forkhead box P1 (Foxp1) transcript levels was observed in all brain regions from postnatal age until old age and could be validated by qPCR. In view of the co-localization and heterodimer formation of FOXP1 with FOXP2, a transcription factor with a well established role for vocalization, and the reported regulation of both alpha-synuclein and FOXP2 expression during avian song learning, we performed a detailed assessment of mouse movements and vocalizations in the postnatal period. While there was no difference in isolation-induced behavioral activity in these animals, the alpha-synuclein-deficient mice exhibited an increased production of isolation-induced ultrasonic vocalizations (USVs). This phenotype might also reflect the reduced expression of the anxiety-related GABA-A receptor subunit gamma 2 (Gabrg2) we observed. Taken together, we identified an early behavioral consequence of alpha-synuclein deficiency and accompanying molecular changes, which supports the notion that the neural connectivity of sound or emotion control systems is affected.
Alpha-synuclein deficiency affects brain Foxp1 expression and ultrasonic vocalization.
Age, Specimen part
View SamplesThe onset of the liver inflamentation in the Sox17+/- embryos.
Sox17 haploinsufficiency results in perinatal biliary atresia and hepatitis in C57BL/6 background mice.
Specimen part
View SamplesOne 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 SamplesOur study in zebrafish is the first to use an animal model to understand the biology of the developmental disorder Roberts Syndrome (RBS). RBS is caused by mutations in the ESCO2 gene.
A zebrafish model of Roberts syndrome reveals that Esco2 depletion interferes with development by disrupting the cell cycle.
Age, Specimen part
View SamplesThe generation of properly functioning gametes in vitro, a key goal in developmental/reproductive biology, requires multi-step reconstitutions of complex germ cell development. Based on the logic of primordial germ cell (PGC)-specification, we demonstrate here the generation of PGC-like cells (PGCLCs) in mice with robust capacity for spermatogenesis from embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) through epiblast-like cells (EpiLCs), a cellular state highly similar to pre-gastrulating epiblasts, but distinct from epiblast stem cells (EpiSCs). The global transcription profiles, epigenetic reprogramming, and cellular dynamics during PGCLC induction from EpiLCs are a meticulous capture of those associated with PGC specification from the epiblasts. Furthermore, we identify Integrin-beta 3 and SSEA1 as markers that purify PGCLCs with spermatogenic capacity free from tumorigenic undifferentiated cells. With the reconstitution of PGC specification pathway from the naive inner cell mass state, our study defines a paradigm for the essential step of in vitro gametogenesis.
Reconstitution of the mouse germ cell specification pathway in culture by pluripotent stem cells.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Sox11 prevents tumorigenesis of glioma-initiating cells by inducing neuronal differentiation.
Specimen part, Cell line
View SamplesFollowing the identification of a critical time window of Blood Brain Barrier formation in the mouse embryo, we aimed to identify genes important for barriergenesis. To this end, we isolated cortical and lung E13.5 endothelial cells and compared expression between the two populations.
Mfsd2a is critical for the formation and function of the blood-brain barrier.
Specimen part
View SamplesTo identify factors involved in tumorigenicity of glioma-initiating cells (GICs), we compared gene expression in GIC-like cells with and without sox11 expression.
Sox11 prevents tumorigenesis of glioma-initiating cells by inducing neuronal differentiation.
Specimen part, Cell line
View SamplesTo identify factors involved in glioma-initiating cells (GICs), we compared gene expression between GIC-like cells and non-GICs.
Sox11 prevents tumorigenesis of glioma-initiating cells by inducing neuronal differentiation.
Specimen part
View Samples