Transcriptome Response and Spatial Pattern of Gene Expression in the Primate Subventricular Zone Neurogenic Niche After Cerebral Ischemia.

The main stem cell niche for neurogenesis in the adult mammalian brain is the subventricular zone (SVZ) that extends along the cerebral lateral ventricles. We aimed at characterizing the initial molecular responses of the macaque monkey SVZ to transient, global cerebral ischemia. We microdissected tissue lining the anterior horn of the lateral ventricle (SVZa) from 7 day post-ischemic and sham-operated monkeys.

A compendium of expression patterns of cholesterol biosynthetic enzymes in the mouse embryo.

Cholesterol and its biosynthetic pathway intermediates and derivatives are required for many developmental processes including membrane biogenesis, transmembrane receptor signaling, steroid biogenesis, nuclear receptor activation, and posttranslational modification of hedgehog (Hh) proteins. To perform such multifaceted tasks depends on stringent regulation of expression of cholesterol biosynthetic enzymes (CBEs). We established for a whole organism, for the first time, the 3D expression pattern of all genes required for cholesterol biosynthesis (CBS), starting from acetyl-CoA and ending with cholesterol.

Being Born Small for Gestational Age Influences Amplitude-Integrated Electroencephalography and Later Outcome in Preterm Infants.

Background: The impact of growth restriction on perinatal morbidity is well known, but electroencephalographic (EEG) data on its influence are still scarce.

Objectives: We aimed to analyze the influence of being born small for gestational age (SGA; defined as a birth weight <10th percentile) on the amplitude-integrated EEG (aEEG) score in the first 2 weeks of life in preterm infants born before 30 weeks of gestation, and its impact on later outcome.

Methods: aEEG data obtained within the first 2 weeks of life on preterm infants born SGA and before 30 weeks of gestational age (GA) were analyzed retrospectively using a combined score [including background activity, occurrence of sleep-wake cycles (SWC) and suspected seizure activity].

A miRNA signature associated with human metastatic medullary thyroid carcinoma.

MicroRNAs (miRNAs) represent a class of small, non-coding RNAs that control gene expression by targeting mRNA and triggering either translational repression or RNA degradation. The objective of our study was to evaluate the involvement of miRNAs in human medullary thyroid carcinoma (MTC) and to identify the markers of metastatic cells and aggressive tumour behaviour. Using matched primary and metastatic tumour samples, we identified a subset of miRNAs aberrantly regulated in metastatic MTC.

Rpl27a mutation in the sooty foot ataxia mouse phenocopies high p53 mouse models.

Ribosomal stress is an important, yet poorly understood, mechanism that results in activation of the p53 tumour suppressor. We present a mutation in the ribosomal protein Rpl27a gene (sooty foot ataxia mice), isolated through a sensitized N-ethyl-N-nitrosourea (ENU) mutagenesis screen for p53 pathway defects, that shares striking phenotypic similarities with high p53 mouse models, including cerebellar ataxia, pancytopenia and epidermal hyperpigmentation. This phenocopy is rescued in a haploinsufficient p53 background.

Excitatory neurons of the proprioceptive, interoceptive, and arousal hindbrain networks share a developmental requirement for Math1.

Hindbrain networks important for sensation and arousal contain diverse neuronal populations with distinct projections, yet share specific characteristics such as neurotransmitter expression. The relationship between the function of these neurons, their developmental origin, and the timing of their migration remains unclear. Mice lacking the proneural transcription factor Math1 (Atoh1) lose neurons essential for hearing, balance, and unconscious proprioception.

Loss of MeCP2 in aminergic neurons causes cell-autonomous defects in neurotransmitter synthesis and specific behavioral abnormalities.

Rett syndrome (RTT) is characterized by specific motor, cognitive, and behavioral deficits. Because several of these abnormalities occur in other disease states associated with alterations in aminergic neurotransmitters, we investigated the contribution of such alterations to RTT pathogenesis. We found that both individuals with RTT and Mecp2-null mice have lower-than-normal levels of aminergic metabolites and content.

Automated pipeline for atlas-based annotation of gene expression patterns: application to postnatal day 7 mouse brain.

Massive amounts of image data have been collected and continue to be generated for representing cellular gene expression throughout the mouse brain. Critical to exploiting this key effort of the post-genomic era is the ability to place these data into a common spatial reference that enables rapid interactive queries, analysis, data sharing, and visualization. In this paper, we present a set of automated protocols for generating and annotating gene expression patterns suitable for the establishment of a database.

Fracture performance of computer-aided manufactured zirconia and alloy crowns.

Objective: To compare the fracture resistance and fracture performance of CAD/CAM zirconia and alloy crowns.

Method And Materials: One electrophoretic deposition alumina ceramic (Wolceram, Wolceram) and 4 zirconia-based systems (ce.novation, ce.

Mouse models of MeCP2 disorders share gene expression changes in the cerebellum and hypothalamus.

A group of post-natal neurodevelopmental disorders collectively referred to as MeCP2 disorders are caused by aberrations in the gene encoding methyl-CpG-binding protein 2 (MECP2). Loss of MeCP2 function causes Rett syndrome (RTT), whereas increased copy number of the gene causes MECP2 duplication or triplication syndromes. MeCP2 acts as a transcriptional repressor, however the gene expression changes observed in the hypothalamus of MeCP2 disorder mouse models suggest that MeCP2 can also upregulate gene expression, given that the majority of genes are downregulated upon loss of MeCP2 and upregulated in its presence.

Identification and subclassification of new Atoh1 derived cell populations during mouse spinal cord development.

At spinal levels, sensory information pertaining to body positioning (proprioception) is relayed to the cerebellum by the spinocerebellar tracts (SCTs). In the past we revealed the basic helix-loop-helix transcription factor Atoh1 (Math1) to be important for establishing Dorsal Progenitor 1 (DP1) commissural interneurons, which comprise a subset of proprioceptive interneurons. Given there exists multiple subdivisions of the SCT we asked whether Atoh1 may also play a role in specifying other cell types in the spinal cord.

Germline mutations in WTX cause a sclerosing skeletal dysplasia but do not predispose to tumorigenesis.

Abnormalities in WNT signaling are implicated in a broad range of developmental anomalies and also in tumorigenesis. Here we demonstrate that germline mutations in WTX (FAM123B), a gene that encodes a repressor of canonical WNT signaling, cause an X-linked sclerosing bone dysplasia, osteopathia striata congenita with cranial sclerosis (OSCS; MIM300373). This condition is typically characterized by increased bone density and craniofacial malformations in females and lethality in males.

miR-19, miR-101 and miR-130 co-regulate ATXN1 levels to potentially modulate SCA1 pathogenesis.

Spinocerebellar ataxia type 1 is caused by expansion of a translated CAG repeat in ataxin1 (ATXN1). The level of the polyglutamine-expanded protein is one of the factors that contributes to disease severity. Here we found that miR-19, miR-101 and miR-130 co-regulate ataxin1 levels and that their inhibition enhanced the cytotoxicity of polyglutamine-expanded ATXN1 in human cells.

Syntaxin 3b is a t-SNARE specific for ribbon synapses of the retina.

Previous studies have demonstrated that ribbon synapses in the retina do not contain the t-SNARE (target-soluble N-ethylmaleimide-sensitive factor attachment protein receptor) syntaxin 1A that is found in conventional synapses of the nervous system. In contrast, ribbon synapses of the retina contain the related isoform syntaxin 3. In addition to its localization in ribbon synapses, syntaxin 3 is also found in nonneuronal cells, where it has been implicated in the trafficking of transport vesicles to the apical plasma membrane of polarized cells.

Bone morphogenetic proteins, eye patterning, and retinocollicular map formation in the mouse.

Patterning events during early eye formation determine retinal cell fate and can dictate the behavior of retinal ganglion cell (RGC) axons as they navigate toward central brain targets. The temporally and spatially regulated expression of bone morphogenetic proteins (BMPs) and their receptors in the retina are thought to play a key role in this process, initiating gene expression cascades that distinguish different regions of the retina, particularly along the dorsoventral axis. Here, we examine the role of BMP and a potential downstream effector, EphB, in retinotopic map formation in the lateral geniculate nucleus (LGN) and superior colliculus (SC).

The insulin-like growth factor pathway is altered in spinocerebellar ataxia type 1 and type 7.

Polyglutamine diseases are inherited neurodegenerative disorders caused by expansion of CAG repeats encoding a glutamine tract in the disease-causing proteins. There are nine disorders, each having distinct features but also clinical and pathological similarities. In particular, spinocerebellar ataxia type 1 and 7 (SCA1 and SCA7) patients manifest cerebellar ataxia with degeneration of Purkinje cells.

The E-protein Tcf4 interacts with Math1 to regulate differentiation of a specific subset of neuronal progenitors.

Proneural factors represent <10 transcriptional regulators required for specifying all of the different neurons of the mammalian nervous system. The mechanisms by which such a small number of factors creates this diversity are still unknown. We propose that proteins interacting with proneural factors confer such specificity.

Mutations in X-linked PORCN, a putative regulator of Wnt signaling, cause focal dermal hypoplasia.

Focal dermal hypoplasia is an X-linked dominant disorder characterized by patchy hypoplastic skin and digital, ocular and dental malformations. We used array comparative genomic hybridization to identify a 219-kb deletion in Xp11.23 in two affected females.

Automated characterization of gene expression patterns with an atlas of the mouse brain.

A spatio-temporal map of gene activity in the brain would be an important contribution to the understanding of brain development, disease, and function. Such a resource is now possible using high-throughput in situ hybridization, a method for transcriptome-wide acquisition of cellular resolution gene expression patterns in serial tissue sections. However, querying an enormous quantity of image data requires computational methods for describing and organizing gene expression patterns in a consistent manner.

Genome-wide atlas of gene expression in the adult mouse brain.

Molecular approaches to understanding the functional circuitry of the nervous system promise new insights into the relationship between genes, brain and behaviour. The cellular diversity of the brain necessitates a cellular resolution approach towards understanding the functional genomics of the nervous system. We describe here an anatomically comprehensive digital atlas containing the expression patterns of approximately 20,000 genes in the adult mouse brain.

Enhanced anxiety and stress-induced corticosterone release are associated with increased Crh expression in a mouse model of Rett syndrome.

Rett syndrome (RTT), a postnatal neurodevelopmental disorder, is caused by mutations in the methyl-CpG-binding protein 2 (MECP2) gene. Children with RTT display cognitive and motor abnormalities as well as autistic features. We studied mice bearing a truncated Mecp2 allele (Mecp2(308/Y) mice) and found evidence of increased anxiety-like behavior and an abnormal stress response as evidenced by elevated serum corticosterone levels.

Diverse patterns of cell-specific gene expression in response to glucocorticoid in the developing small intestine.

Although glucocorticoids are known to elicit functional maturation of the gastrointestinal tract, the molecular mechanisms of glucocorticoid action on the developing intestine have not been fully elucidated. Our previous microarray studies identified 66 transcripts as being rapidly induced in the jejunum following dexamethasone (Dex) administration to suckling mice. Now we report the specific cellular location of a subset of these transcripts.

Hybrid segmentation framework for tissue images containing gene expression data.

Associating specific gene activity with functional locations in the brain results in a greater understanding of the role of the gene. To perform such an association for the over 20,000 genes in the mammalian genome, reliable automated methods that characterize the distribution of gene expression in relation to a standard anatomical model are required. In this work, we propose a new automatic method that results in the segmentation of gene expression images into distinct anatomical regions in which the expression can be quantified and compared with other images.

Comprehensive analysis of the expression patterns of the adenylate cyclase gene family in the developing and adult mouse brain.

Adenylate cyclases (Adcys) are components of several developmentally, neurophysiologically, and pharmacologically relevant signaling pathways. A prominent feature of Adcys is their ability to integrate multiple signaling pathways into a single second messenger pathway, the production of cAMP. Nine isoforms of membrane-bound Adcys are known, each encoded by a distinct gene.