Hirschsprung disease (HSCR, MIM ♯142623) is a multigenic neuocristopathy (neural crest disorder) characterized by absence of enteric ganglia in a variable portion of the distal colon. Subsets of HSCR individuals also present with neural crest-derived melanocyte deficiencies (Hirschsprung-Waardenburg, HSCR-WS, MIM ♯277580). Murine models have been instrumental in the identification and analysis of HSCR disease genes. These include mice with deficiencies of endothelin B receptor (Ednrb^s–l refs 1,2) endothelin 3 (Edn3ls; refs 1,3) the tyrosine kinase receptor cftet4 and glial-derived neurotrophic factor5–7. Another mouse model of HSCR disease, Dom, arose spontaneously at the Jackson Laboratory8. While Dom/+ heterozygous mice display regional deficiencies of neural crest–derived enteric ganglia in the distal colon, Dom/Dom homozygous animals are embryonic lethal8. We have determined that premature termination of SOX10, a member of the SflV–like HMG box family of transcription factors, is responsible for absence of the neural crest derivatives in Dom mice. We demonstrate expression of SOX10 in normal neural crest cells, disrupted expression of both SOX10 and the HSCR disease gene Ednrb in Dom mutant embryos, and loss of neural crest derivatives due to apoptosis. Our studies suggest that SOX10 is essential for proper peripheral nervous system development. We propose SOX10 as a candidate disease gene for individuals with HSCR whose disease does not have an identified genetic origin.

The GenitoUrinary Development Molecular Anatomy Project (GUDMAP) is an international consortium working to generate gene expression data and transgenic mice. GUDMAP includes data from large-scale in situ hybridisation screens (wholemount and section) and microarray gene expression data of microdissected, laser-captured and FACS-sorted components of the developing mouse genitourinary (GU) system. These expression data are annotated using a high-resolution anatomy ontology specific to the developing murine GU system. GUDMAP data are freely accessible at www.gudmap.org via easy-to-use interfaces. This curated, high-resolution dataset serves as a powerful resource for biologists, clinicians and bioinformaticians interested in the developing urogenital system. This paper gives examples of how the data have been used to address problems in developmental biology and provides a primer for those wishing to use the database in their own research.

Significance: The demonstration of a robust neurogenesis program in the adult gut and the existence of an enteric neural precursor cell (ENPC) responsible for the same has profound biological and clinical implications. This demonstrates the presence of robust adult neurogenesis outside of the CNS, and indicates the vulnerability of the enteric nervous system to exogenous influences, even in adults. As an example, it is possible that acquired diseases of the enteric nervous system, such as achalasia, may result from a loss of ENPC, analogous to congenital disorders, such as Hirschsprung’s. The ability to identify the adult ENPC will therefore enable a new understanding of the pathogenesis of enteric neuromuscular diseases as well as the development of novel regenerative therapies.

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.