Canonical Wnt signaling regulates Nkx3.1 expression and luminal epithelial differentiation during prostate organogenesis.
Canonical Wnt signaling regulates Nkx3.1 expression and luminal epithelial differentiation during prostate organogenesis.
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DOI：
10.1002/dvdy.24008
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发表时间：
2013-10
影响因子：
2.5
通讯作者：
Shen, Michael M.
中科院分区：
文献类型：
--
作者：
Kruithof-de Julio, Marianna;Shibata, Maho;Desai, Nishita;Reynon, Melissa;Halili, M. Vivienne;Hu, Ya-Ping;Price, Sandy M.;Abate-Shen, Cory;Shen, Michael M.
前列腺的形成需要胚胎尿生殖窦（UGS）的上皮和间充质成分之间的相互作用。然而，介导这些相互作用的信号传导因子的身份在很大程度上是未知的。我们的研究表明，前列腺特异性转录因子Nkx3.1的表达受经典Wnt信号通路的调节。使用携带靶向lacZ基因敲入等位基因Nkx3.1的小鼠，我们发现Nkx3.1在前列腺器官发生过程中在导管芽的所有上皮细胞中表达。在泌尿生殖窦外植体培养物中加入Wnt抑制剂大大减少了前列腺出芽，并抑制了Nkx3.1表达以及管腔上皮细胞的分化。对TCF/Lef：H2 B-GFP转基因报告基因的分析表明，在前列腺形成之前，在尿生殖间充质中发现了典型的Wnt信号传导活性，但在尿生殖窦上皮中没有发现，并且随后在前列腺导管尖端的间充质和上皮中观察到。此外，TCF/Lef：H2 B-GFP报告基因活性在Nkx3.1缺失的新生儿前列腺的上皮细胞中降低，表明Nkx3.1在发育中的前列腺芽尖中起维持经典Wnt信号传导活性的作用。我们认为，激活的经典Wnt信号和Nkx3.1功能的正反馈回路，以调节前列腺芽的生长和管腔上皮分化。
The formation of the prostate gland requires reciprocal interactions between the epithelial and mesenchymal components of the embryonic urogenital sinus (UGS). However, the identity of the signaling factors that mediate these interactions is largely unknown. Our studies show that expression of the prostate-specific transcription factor Nkx3.1 is regulated by the canonical Wnt signaling pathway. Using mice carrying a targeted lacZ knock-in allele of Nkx3.1, we find that Nkx3.1 is expressed in all epithelial cells of ductal buds during prostate organogenesis. Addition of Wnt inhibitors to urogenital sinus explant culture greatly reduces prostate budding and inhibits Nkx3.1 expression as well as differentiation of luminal epithelial cells. Analyses of a TCF/Lef:H2B-GFP transgene reporter show that canonical Wnt signaling activity is found in urogenital mesenchyme but not urogenital sinus epithelium prior to prostate formation, and is later observed in the mesenchyme and epithelium of prostate ductal tips. Furthermore, TCF/Lef:H2B-GFP reporter activity is reduced in epithelial cells of Nkx3.1 null neonatal prostates, suggesting that Nkx3.1 functions to maintain canonical Wnt signaling activity in developing prostate bud tips. We propose that activated canonical Wnt signals and Nkx3.1 function in a positive feedback loop to regulate prostate bud growth and luminal epithelial differentiation.
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影响因子：
2.5
作者：
Mehta, Vatsal;Abler, Lisa L.;Keil, Kimberly P.;Schmitz, Christopher T.;Joshi, Pinak S.;Vezina, Chad M.
通讯作者：
Vezina, Chad M.
影响因子：
2.5
作者：
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通讯作者：
Bieberich, CJ
影响因子：
2.7
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Berman, DM;Desai, N;Shen, MM
通讯作者：
Shen, MM
影响因子：
2.7
作者：
Donjacour, AA;Thomson, AA;Cunha, GR
通讯作者：
Cunha, GR
影响因子：
2.7
作者：
Bridgewater, Darren;Cox, Brian;Rosenblum, Norman D.
通讯作者：
Rosenblum, Norman D.