title: WNT5A selectively inhibits mouse ventral prostate development.
abstract: The establishment of prostatic budding patterns occurs early in prostate development but mechanisms responsible for this event are poorly understood. We investigated the role of WNT5A in patterning prostatic buds as they emerge from the fetal mouse urogenital sinus (UGS). Wnt5a mRNA was expressed in UGS mesenchyme during budding and was focally up-regulated as buds emerged from the anterior, dorsolateral, and ventral UGS regions. We observed abnormal UGS morphology and prostatic bud patterns in Wnt5a null male fetuses, demonstrated that prostatic bud number was decreased by recombinant mouse WNT5A protein during wild type UGS morphogenesis in vitro, and showed that ventral prostate development was selectively impaired when these WNT5A-treated UGSs were grafted under under kidney capsules of immunodeficient mice and grown for 28 d. Moreover, a WNT5A inhibitory antibody, added to UGS organ culture media, rescued prostatic budding from inhibition by a ventral prostatic bud inhibitor, 2,3,8,7-tetrachlorodibenzo-p-dioxin, and restored ventral prostate morphogenesis when these tissues were grafted under immunodeficient mouse kidney capsules and grown for 28 d. These results suggest that WNT5A participates in prostatic bud patterning by restricting mouse ventral prostate development.
authors.affiliation: Molecular and Environmental Toxicology Center, University of Wisconsin, Madison, WI 53705, USA.
authors.forename: Sarah Hicks
authors.initials: SH
authors.lastname: Allgeier
authors.forename: Tien-Min
authors.initials: TM
authors.lastname: Lin
authors.forename: Chad M
authors.initials: CM
authors.lastname: Vezina
authors.forename: Robert W
authors.initials: RW
authors.lastname: Moore
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Fritz
authors.forename: Shing-Yan
authors.initials: SY
authors.lastname: Chiu
authors.forename: ChuanLi
authors.initials: C
authors.lastname: Zhang
authors.forename: Richard E
authors.initials: RE
authors.lastname: Peterson
mesh_terms: D000818:Animals; D019521:Body Patterning; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D038081:Organogenesis; D011467:Prostate / Q000196:embryology* / Q000378:metabolism; D046509:Tissue Culture Techniques; D051153:Wnt Proteins / Q000502:physiology*; D000071818:Wnt-5a Protein
chemical_list: D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse