A Role for Notch Signaling in Stromal Survival and Differentiation during Prostate Development
A Role for Notch Signaling in Stromal Survival and Differentiation during Prostate Development
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DOI：
10.1210/en.2008-0383
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发表时间：
2009-01-01
期刊：
影响因子：
4.8
通讯作者：
Thomson, Axel A.
中科院分区：
文献类型：
--
作者：
Orr, Brigid;Grace, O. Cathal;Thomson, Axel A.
Notch 1信号参与前列腺上皮的生长和分化，我们已经研究了Notch信号在发育中的前列腺基质中的作用。我们最初在前列腺间充质的基因谱研究中观察到δ样1（Dlk 1）和Notch 2的表达，并预计它们可能在诱导间充质的关键子集中表达。使用定量RT-PCR，北方印迹，和整体安装在原位杂交，我们证实，Dlk 1和Notch 2的mRNA表现出有限的表达模式在前列腺发育过程中的基质的子集。Dlk 1和Notch 2蛋白的定位反映了转录本的表达，并在基质中显示出不同和重叠的表达模式。Dlk 1和Notch 2共表达于腹侧间充质垫（VMP）的浓缩诱导间充质中，并且部分共定位于尿道基质的平滑肌（SM）层。Dlk 1在女性尿道VMP附近的SM中不表达。使用前列腺雏形的器官培养物和notch受体活性的小分子抑制剂检查notch信号传导的功能。notch信号的抑制导致前列腺和雌性VMP培养物中基质组织的损失，表明该途径是基质存活所需的。notch信号的抑制也导致上皮和基质分化的变化，这在体外生长的前列腺中SM α-肌动蛋白和p63的分布改变中是明显的。notch信号对基质的影响仅在睾酮存在下明显，与对上皮分化的影响相反。内分泌学150：463-472，2009）
Notch1 signaling is involved in epithelial growth and differentiation of prostate epithelia, and we have examined the role that notch signaling plays in the stroma of the developing prostate. We initially observed expression of delta-like 1 (Dlk1) and Notch2 in gene profiling studies of prostatic mesenchyme, and anticipated that they might be expressed in a key subset of inductive mesenchyme. Using quantitative RT-PCR, Northern blotting, and whole mount in situ hybridization, we confirmed that both Dlk1 and Notch2 mRNAs showed a restricted expression pattern within subsets of the stroma during prostate development. Localization of Dlk1 and Notch2 proteins mirrored the transcript expression, and showed both distinct and overlapping expression patterns within the stroma. Dlk1 and Notch2 were coexpressed in condensed inductive mesenchyme of the ventral mesenchymal pad (VMP), and were partially colocalized in the smooth muscle (SM) layer of the urethral stroma. In addition, Dlk1 was not expressed in SM adjacent to the VMP in female urethra. The function of notch signaling was examined using organ cultures of prostate rudiments and a small molecule inhibitor of notch receptor activity. Inhibition of notch signaling led to a loss of stromal tissue in both prostate and female VMP cultures, suggesting that this pathway was required for stromal survival. Inhibition of notch signaling also led to changes in both epithelial and stromal differentiation, which was evident in altered distributions of SM alpha-actin and p63 in prostates grown in vitro. The effects of notch signaling upon the stroma were only evident in the presence of testosterone, in contrast to effects upon epithelial differentiation. Endocrinology 150: 463-472, 2009)