title: Molecular Characterization of the Genital Organizer: Gene Expression Profile of the Mouse Urethral Plate Epithelium.
abstract: OBJECTIVE
  Lower urinary tract malformations are among the most common congenital anomalies in humans. Molecular genetic studies of mouse external genital development have begun to identify mechanisms that pattern the genital tubercle and orchestrate urethral tubulogenesis. The urethral plate epithelium is an endodermal signaling region that has an essential role in external genital development. However, little is known about the molecular identity of this cell population or the genes that regulate its activity.
  
  
  METHODS
  We used microarray analysis to characterize differences in gene expression between urethral plate epithelium and surrounding tissue in mouse genital tubercles. In situ hybridizations were performed to map gene expression patterns and ToppCluster (https://toppcluster.cchmc.org/) was used to analyze gene associations.
  
  
  RESULTS
  A total of 84 genes were enriched at least 20-fold in urethral plate epithelium relative to surrounding tissue. The majority of these genes were expressed throughout the urethral plate in males and females at embryonic day 12.5 when the urethral plate is known to signal. Functional analysis using ToppCluster revealed genetic pathways with known functions in other organ systems but unknown roles in external genital development. Additionally, a 3-dimensional molecular atlas of genes enriched in urethral plate epithelium was generated and deposited at the GUDMAP (GenitoUrinary Development Molecular Anatomy Project) website (http://gudmap.org/).
  
  
  CONCLUSIONS
  We identified dozens of genes previously unknown to be expressed in urethral plate epithelium at a crucial developmental period. It provides a novel panel of genes for analysis in animal models and in humans with external genital anomalies.
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida Genetics Institute, University of Florida, Gainesville, Florida.
authors.forename: Brooke A
authors.initials: BA
authors.lastname: Armfield
authors.affiliation: Department of Biology, University of Florida Genetics Institute, University of Florida, Gainesville, Florida.
authors.forename: Ashley W
authors.initials: AW
authors.lastname: Seifert
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida Genetics Institute, University of Florida, Gainesville, Florida.
authors.forename: Zhengui
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida Genetics Institute, University of Florida, Gainesville, Florida.
authors.forename: Emily M
authors.initials: EM
authors.lastname: Merton
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida Genetics Institute, University of Florida, Gainesville, Florida.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Rock
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida Genetics Institute, University of Florida, Gainesville, Florida.
authors.forename: Maria-Cecilia
authors.initials: MC
authors.lastname: Lopez
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida Genetics Institute, University of Florida, Gainesville, Florida.
authors.forename: Henry V
authors.initials: HV
authors.lastname: Baker
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida Genetics Institute, University of Florida, Gainesville, Florida; Department of Biology, University of Florida Genetics Institute, University of Florida, Gainesville, Florida; Howard Hughes Medical Institute, University of Florida Genetics Institute, University of Florida, Gainesville, Florida. Electronic address: MJCohn@ufl.edu.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Cohn
mesh_terms: D000818:Animals; D005260:Female; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000096:biosynthesis / Q000235:genetics*; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D023421:Models, Animal; D040081:Protein Array Analysis; D012313:RNA / Q000235:genetics*; D015398:Signal Transduction; D014521:Urethra / Q000196:embryology* / Q000378:metabolism; D019459:Urothelium / Q000196:embryology* / Q000378:metabolism
chemical_list: D053823:Hedgehog Proteins; D012313:RNA
keywords: congenital abnormalities; gene expression; genitalia; microarray analysis; urethra