Allgeier Sarah Hicks, Lin Tien-Min, Vezina Chad M, Moore Robert W, Fritz Wayne A, Chiu Shing-Yan, Zhang ChuanLi, Peterson Richard E
Molecular and Environmental Toxicology Center, University of Wisconsin, Madison, WI 53705, USA.
Dev Biol. 2008 Dec 1;324(1):10-7. doi: 10.1016/j.ydbio.2008.08.018. Epub 2008 Aug 29.
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.
前列腺芽生模式的建立在前列腺发育早期就已发生，但导致这一过程的机制尚不清楚。我们研究了WNT5A在前列腺芽从胎鼠泌尿生殖窦（UGS）中长出时对其模式形成的作用。在芽生过程中，Wnt5a mRNA在UGS间充质中表达，并且随着芽从前部、背外侧和腹侧UGS区域长出而局部上调。我们在Wnt5a基因敲除的雄性胎儿中观察到UGS形态异常和前列腺芽模式异常，证明在体外野生型UGS形态发生过程中，重组小鼠WNT5A蛋白会减少前列腺芽的数量，并且表明当将这些经WNT5A处理的UGS移植到免疫缺陷小鼠的肾包膜下并生长28天时，腹侧前列腺发育受到选择性损害。此外，添加到UGS器官培养基中的WNT5A抑制性抗体可使前列腺芽生免受腹侧前列腺芽抑制剂2,3,8,7-四氯二苯并对二恶英的抑制，并且当将这些组织移植到免疫缺陷小鼠的肾包膜下并生长28天时，可恢复腹侧前列腺形态发生。这些结果表明，WNT5A通过限制小鼠腹侧前列腺发育参与前列腺芽模式形成。
