title: Embryonic origin and remodeling of the urinary and digestive outlets.
abstract: Separating digestive and urinary outlets is a critical step during mammalian embryogenesis. However, the natural history of these structures is poorly studied, and little is known about their embryonic origin. Here, we show that peri-cloacal mesenchymal (PCM) progenitors are the major source of these structures. Surprisingly, PCM progenitors also contribute to perineum, a structural barrier separating the urinary and digestive tracts, suggesting a potential role of PCM progenitors in establishing independent urinary and digestive outlets. We demonstrate that Six1 and Six2 are complementarily but asymmetrically expressed in the PCM progenitors. Deletion of these genes results in decreased cell survival and proliferation, and consequently in agenesis of the perineum and severe hypoplasia of the genital tubercle. Together, these findings suggest that PCM progenitors are the unexpected source of perineum and genital tubercle, and establish a basic framework for investigating normal and abnormal development of anorectal and genitourinary structures.
authors: Department of Urology, Boston Children's Hospital, Boston, Massachusetts, USA.
authors: Chen
authors: C
authors: Wang
authors: JingYing
authors: J
authors: Wang
authors: Joseph G
authors: JG
authors: Borer
authors: Xue
authors: X
authors: Li
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics; D002988:Cloaca / Q000196:embryology*; D004622:Embryo, Mammalian; D005260:Female; D041981:Gastrointestinal Tract / Q000196:embryology*; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D005836:Genitalia, Female / Q000196:embryology*; D005837:Genitalia, Male / Q000196:embryology*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D010502:Perineum / Q000196:embryology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014551:Urinary Tract / Q000196:embryology*
chemical_list: D018398:Homeodomain Proteins; C490947:Six1 protein, mouse; C497420:Six2 protein, mouse; D014157:Transcription Factors
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