Insights into olfactory ensheathing cell development from a laser-microdissection and transcriptome-profiling approach.

Olfactory ensheathing cells (OECs) are neural crest-derived glia that ensheath bundles of olfactory axons from their peripheral origins in the olfactory epithelium to their central targets in the olfactory bulb. We took an unbiased laser microdissection and differential RNA-seq approach, validated by in situ hybridization, to identify candidate molecular mechanisms underlying mouse OEC development and differences with the neural crest-derived Schwann cells developing on other peripheral nerves. We identified 25 novel markers for developing OECs in the olfactory mucosa and/or the olfactory nerve layer surrounding the olfactory bulb, of which 15 were OEC-specific (that is, not expressed by Schwann cells). One pan-OEC-specific gene, Ptprz1, encodes a receptor-like tyrosine phosphatase that blocks oligodendrocyte differentiation. Mutant analysis suggests Ptprz1 may also act as a brake on OEC differentiation, and that its loss disrupts olfactory axon targeting. Overall, our results provide new insights into OEC development and the diversification of neural crest-derived glia.Cambridge Commonwealth Trust Cambridge Philosophical Societ

GUDMAP - An Online GenitoUrinary Resource

The GenitoUrinary Development Molecular Anatomy Project (GUDMAP) is a consortium of laboratories working to provide the scientific and medical community with gene expression data and tools to facilitate research (see "www.gudmap.org":http://www.gudmap.org). The data provided by GUDMAP includes large _in situ_ hybridization screens (wholemount and section) and expression microarray analysis of components of the developing mouse urogenital system (including laser-captured material and FACS-isolated cells from transgenic reporter mice). In addition, a high-resolution anatomy ontology has been developed by members of the GUDMAP consortium to describe the subcompartments of the developing murine genitourinary tract. 

The GUDMAP Database Development Team and Editorial Office - both based in Edinburgh - function to ensure submission, curation, storage and presentation of the data submitted by the GUDMAP consortium. Our collective aim is twofold: 1) to simplify the process of submission so that data is publically available as soon as it is produced; and 2) to organize this information in a database and ensure that the online interface is continuously available and easy to use. Thus far, we have developed a range of tools that help both the submitter and the end user. These include: an online annotation tool that simplifies _in situ_ data submission through an ontology-based graphical user interface; a database interface that allows users to browse and query expression data, and to filter data by organ system; a heat-map display of microarray data and analyses. Furthermore, the Edinburgh team has developed a GUDMAP Disease Database that queries associations between genes, genitourinary diseases, and renal/urinary and reproductive phenotypes. In collaboration with GUDMAP consortium members at the CCHMC (Cincinnati Children's Hospital Medical Center), the Disease Database is being extended to include mammalian phenotypes mapped to OMIM entries. 

By virtue of its impressive dataset and its ease of use we hope that the GUDMAP Website will continue to serve as a powerful resource for biologists, clinicians and bioinformaticians with an interest in the urogenital system

Tabou

Program for the fifth annual RISD Cabaret held in the Waterman Building. Design and layout by Nonie Close.https://digitalcommons.risd.edu/liberalarts_cabaret_programs/1004/thumbnail.jp

An illustrated anatomical ontology of the developing mouse lower urogenital tract

Malformation of the urogenital tract represents a considerable paediatric burden, with many defects affecting the lower urinary tract (LUT), genital tubercle and associated structures. Understanding the molecular basis of such defects frequently draws on murine models. However, human anatomical terms do not always superimpose on the mouse, and the lack of accurate and standardised nomenclature is hampering the utility of such animal models. We previously developed an anatomical ontology for the murine urogenital system. Here, we present a comprehensive update of this ontology pertaining to mouse LUT, genital tubercle and associated reproductive structures (E10.5 to adult). Ontology changes were based on recently published insights into the cellular and gross anatomy of these structures, and on new analyses of epithelial cell types present in the pelvic urethra and regions of the bladder. Ontology changes include new structures, tissue layers and cell types within the LUT, external genitalia and lower reproductive structures. Representative illustrations, detailed text descriptions and molecular markers that selectively label muscle, nerves/ganglia and epithelia of the lower urogenital system are also presented. The revised ontology will be an important tool for researchers studying urogenital development/malformation in mouse models and will improve our capacity to appropriately interpret these with respect to the human situation

Enteric Neuron Imbalance and Proximal Dysmotility in Ganglionated Intestine of the Sox10Dom/+ Hirschsprung Mouse ModelSummary

Background & Aims: In Hirschsprung disease (HSCR), neural crest-derived progenitors (NCPs) fail to completely colonize the intestine so that the enteric nervous system is absent from distal bowel. Despite removal of the aganglionic region, many HSCR patients suffer from residual intestinal dysmotility. To test the hypothesis that inappropriate lineage segregation of NCPs in proximal ganglionated regions of the bowel could contribute to such postoperative disease, we investigated neural crest (NC)-derived lineages and motility in ganglionated, postnatal intestine of the Sox10Dom/+ HSCR mouse model. Methods: Cre-mediated fate-mapping was applied to evaluate relative proportions of NC-derived cell types. Motility assays were performed to assess gastric emptying and small intestine motility while colonic inflammation was assessed by histopathology for Sox10Dom/+ mutants relative to wild-type controls. Results: Sox10Dom/+ mice showed regional alterations in neuron and glia proportions as well as calretinin+ and neuronal nitric oxide synthase (nNOS)+ neuronal subtypes. In the colon, imbalance of enteric NC derivatives correlated with the extent of aganglionosis. All Sox10Dom/+ mice exhibited reduced small intestinal transit at 4 weeks of age; at 6 weeks of age, Sox10Dom/+ males had increased gastric emptying rates. Sox10Dom/+ mice surviving to 6 weeks of age had little or no colonic inflammation when compared with wild-type littermates, suggesting that these changes in gastrointestinal motility are neurally mediated. Conclusions: The Sox10Dom mutation disrupts the balance of NC-derived lineages and affects gastrointestinal motility in the proximal, ganglionated intestine of adult animals. This is the first report identifying alterations in enteric neuronal classes in Sox10Dom/+ mutants, which suggests a previously unrecognized role for Sox10 in neuronal subtype specification. Keywords: Aganglionosis, Enteric Nervous System, Neural Cres

Coordinate control and variation in X-linked gene expression among female mice

In normal female mammals, one of the two X Chromosome (Chr) homologs per cell is silenced coordinately during early embryogenesis. The genes located on the inactivated X homolog are predicted to be influenced by the same underlying repression mechanism. To test the uniformity of cis -acting gene repression, 32 genetically identical F 1 female mice were analyzed for differential expression of homologous alleles at three X-linked genes— Otc, Atp7a (=Mottled), and Hprt. Gene expression was assayed by the single-nucleotide primer extension (SNuPE) method, thereby allowing the three genes to be quantitated from the same RNA sample. Although variable between individual animals, the relative expression of the two alleles ( allelic expression ratio ) of the genes is significantly correlated within each steady-state RNA pool. When examined by animal age (3 months to 12 months), no statistically significant differences were observed in the mean or variance of allelic expression ratio. Together, the results confirm that X inactivation is coordinately controlled and is stable across the early- to mid-adult life span.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42137/1/335-8-11-818_8n11p818.pd