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Cohn Group | GenitoUrinary Development Molecular Anatomy Project (GUDMAP)
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Cohn Group

Marty Cohn (PI)
University of Florida

  • Brooke Armfield
    University of Florida
  • Julia Bittencourt
    University of Florida

Project Description

RELATED DATA

Building on our GUDMAP2 project, which focused on the dorsoventral (D-V) axis of the LUT, this study aims to identify and map the molecular regionalization of cells along the A-P axis of the mouse and human urethra, from the bladder to the urethral meatus. Our goal is to generate the foundation of data necessary to study how cell type identity along the urethra relates to development of congenital defects, such as urethral valves, enlarged prostatic utricle, urethral polyps, strictures, and agenesis of urethral structures.

Publications

  1. Molecular characterization of the genital organizer: Gene expression profile of the mouse urethral plate epithelium.

    Armfield, BA; Seifert, AW; Zheng, Z; Merton, EM; Rock, JR; Lopez, MC; Baker, HV; Cohn, MJ. J Urol. vol. 196(4), 1295–302. October 2016.

  2. An illustrated anatomical ontology of the developing mouse lower urogenital tract

    Georgas, KM; Armstrong, J; Keast, JR; Larkins, CE; McHugh, KM; Southard-Smith, EM; Cohn, MJ; Batourina, E; Dan, H; Schneider, K; Buehler, DP; Wiese, CB; Brennan, J; Davies, JA; Harding, SD; Baldock, RA; Little, MH; Vezina, CM; Mendelsohn, C. Development. vol. 142(10), 1893–908. May 2015.

    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.

  3. Embryonic origin and compartmental organization of the external genitalia

    Herrera, AM; Cohn, MJ. Sci Rep. vol. 4, 6896. November 2014.

    Genital malformations occur at a high frequency in humans, affecting ~1:250 live births. The molecular mechanisms of external genital development are beginning to be identified; however, the origin of cells that give rise to external genitalia is unknown. Here we use cell lineage analysis to show that the genital tubercle, the precursor of the penis and clitoris, arises from two populations of progenitor cells that originate at the lateral edges of the embryo, at the level of the posterior hindlimb buds and anterior tail. During body wall closure, the left and right external genital progenitor pools are brought together at the ventral midline, where they form the paired genital swellings that give rise to the genital tubercle. Unexpectedly, the left and right external genital progenitor pools form two lineage-restricted compartments in the phallus. Together with previous lineage studies of limb buds, our results indicate that, at the pelvic level, the early lateral mesoderm is regionalized from medial to lateral into dorsal limb, ventral limb, and external genital progenitor fields. These findings have implications for the evolutionary diversification of external genitalia and for the association between external genital defects and disruption of body wall closure, as seen in the epispadias-extrophy complex.