Lee Kevin, Jeong JaeWook, Kwak Inseok, Yu Cheng-Tai, Lanske Beate, Soegiarto Desi W, Toftgard Rune, Tsai Ming-Jer, Tsai Sophia, Lydon John P, DeMayo Francesco J
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Nat Genet. 2006 Oct;38(10):1204-9. doi: 10.1038/ng1874. Epub 2006 Sep 3.
The hedgehog family of morphogens are regulators of cell proliferation, differentiation and cell-cell communication. These morphogens have been shown to have important roles in organogenesis, spermatogenesis, stem cell maintenance and oncogenesis. Indian hedgehog (encoded by Ihh) has been shown to be expressed in the uterine epithelium under the control of the steroid hormone, progesterone. Although in vivo and in vitro studies have shown that progesterone achieves its effects on uterine function through epithelial-stromal cross-talk, molecular mediator(s) for this cellular communication pathway have not been elucidated. Using new experimental approaches that ablate Ihh specifically in Pgr-positive uterine cells of the mouse, we demonstrate that Ihh is an essential mediator of Pgr action in the uterus, and expression of this factor is critical in mediating the communication between the uterine epithelium and stroma required for embryo implantation.
形态发生素的刺猬家族是细胞增殖、分化和细胞间通讯的调节因子。这些形态发生素已被证明在器官发生、精子发生、干细胞维持和肿瘤发生中发挥重要作用。印度刺猬因子(由Ihh编码)已被证明在类固醇激素孕酮的控制下在子宫上皮中表达。尽管体内和体外研究表明孕酮通过上皮-基质相互作用实现其对子宫功能的影响,但这种细胞通讯途径的分子介质尚未阐明。使用新的实验方法在小鼠Pgr阳性子宫细胞中特异性消融Ihh,我们证明Ihh是孕酮在子宫中作用的必需介质,并且该因子的表达对于介导胚胎着床所需的子宫上皮和基质之间的通讯至关重要。