BMP7 inhibits branching morphogenesis in the prostate gland and interferes with Notch signaling
BMP7 inhibits branching morphogenesis in the prostate gland and interferes with Notch signaling
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DOI：
10.1016/j.ydbio.2005.08.018
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发表时间：
2005-12-15
影响因子：
2.7
通讯作者：
Walden, PD
中科院分区：
文献类型：
--
作者：
Grishina, IB;Kim, SY;Walden, PD
小鼠前列腺通过来自泌尿生殖上皮和间充质的分支形态发生而发育。雄激素和发育因子，包括FGF 10和SHH，促进前列腺生长（Berman，D.M.，德赛N.，王，X.，Karhadkar，S.S.，Reynon，M.，Abate-Shen，C.，宾夕法尼亚州比奇市，Shen，M.M.，2004. Hedgehog信号在雄激素产生和前列腺导管形态发生中的作用。Dev. 267，387 -398; Donjacour，A.A.，Thomson，A.A.，库尼亚，G.R.，2003. FGF-10在胎儿前列腺的生长中起重要作用。Dev. 261，39-54），而来自间充质的BMP 4信号传导已显示抑制前列腺分支（Lamm. M. L.，波德拉塞克CA，巴内特。戴·赫，李，J.，克莱门斯，J.Q.，Hebner，C.M.，布什曼，W.，2001.间充质因子骨形态发生蛋白4限制发育中前列腺的导管出芽和分支形态发生。Dev. 232，301-314）。在这里，我们表明骨形态发生蛋白7（BMP 7）限制前列腺上皮的分支。BMP 7在前列腺芽形成之前在尿道周围的泌尿生殖间质中表达，随后在前列腺上皮中表达。我们发现，BMP 7（lacZAacZ）空前列腺显示前列腺分支的两倍增加，而重组BMP 7在器官培养中以浓度依赖性方式抑制前列腺形态发生。我们进一步探讨的机制，发育信号可能被解释在泌尿生殖上皮细胞调节分支形态发生。我们发现Notch 1活性与前列腺芽的形成有关，并且Notch 1信号在BMP 7无效的泌尿生殖上皮中被去抑制。基于我们的研究，我们提出了一个模型，BMP 7抑制前列腺中的分支形态发生，并限制了具有高Notch 1/Hes 1活性的结构域的数量。(c)2005年爱思唯尔公司All rights reserved.
The mouse prostate gland develops by branching morphogenesis from the urogenital epithelium and mesenchyme, Androgens and developmental factors, including FGF10 and SHH, promote prostate growth (Berman, D.M., Desai. N.,Wang, X., Karhadkar, S.S., Reynon, M., Abate-Shen, C., Beachy, P.A., Shen, M.M., 2004. Roles for Hedgehog signaling in androgen production and prostate ductal morphogenesis. Dev. Biol. 267,387-398; Donjacour, A.A., Thomson, A.A., Cunha, G.R., 2003. FGF-10 plays an essential role in the growth of the fetal prostate. Dev. Biol. 261, 39-54), while BMP4 signaling from the mesenchyme has been shown to suppresses prostate branching (Lamm. M.L., Podlasek. C.A., Barnett. D.H., Lee, J., Clemens, J.Q., Hebner, C.M., Bushman, W., 2001. Mesenchymal factor bone morphogenetic protein 4 restricts ductal budding and branching morphogenesis in the developing prostate. Dev. Biol. 232, 301-314). Here, we show that Bone Morphogenetic Protein 7 (BMP7) restricts branching of the prostate epithelium. BMP7 is expressed in the periurethral urogenital mesenehyme prior to formation of the prostate buds and, subsequently, in the prostate epithelium. We show that BMP7(lacZAacZ) null prostates show a two-fold increase in prostate branching, while recombinant BMP7 inhibits prostate morphogenesis in organ culture in a concentration-dependent manner. We further explore the mechanisms by which the developmental signals may be interpreted in the urogenital epithelium to regulate branching morphogenesis. We show that Notch1 activity is associated with the formation of the prostate buds, and that Notch1 signaling is derepressed in BMP7 null urogenital epithelium. Based on our studies, we propose a model that BMP7 inhibits branching morphogenesis in the prostate and limits the number of domains with high Notch1/Hes1 activity. (c) 2005 Elsevier Inc. All rights reserved.