Cross-talk between fibroblast growth factor and bone morphogenetic proteins regulates gap junction-mediated intercellular communication in lens cells
Cross-talk between fibroblast growth factor and bone morphogenetic proteins regulates gap junction-mediated intercellular communication in lens cells
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DOI：
10.1091/mbc.e08-02-0124
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发表时间：
2008-06-01
影响因子：
3.3
通讯作者：
Musil, Linda S.
中科院分区：
文献类型：
--
作者：
Boswell, Bruce A.;Lein, Pamela J.;Musil, Linda S.
透镜中的稳态依赖于细胞间缝隙连接通道的广泛网络。间隙连接介导的细胞间耦合（GJIC）在透镜的赤道区域比在任何一极都高，这是一种被认为对透镜透明度至关重要的不对称性。鸡胚透镜上皮细胞的原代培养物响应于纯化的成纤维细胞生长因子（FGF）1/2或玻璃体调节的培养基上调GJIC，玻璃体是透镜赤道部的因子（包括FGF）的主要储库。我们发现，纯化的骨形态发生蛋白（BMP）2，-4，和-7也上调GJIC在这些文化。BMP 2、BMP-4或两者都存在于玻璃体条件培养基中，BMP 4和BMP-7由透镜细胞内源性表达。值得注意的是，晶状体衍生的BMP信号传导是纯化的FGF上调GJIC所必需的，并且足以被玻璃体液上调。这是第一次证明在postplacode透镜细胞中FGF和BMP之间的强制性相互作用，以及FGF/BMP串扰在任何细胞类型中调节GJIC的作用。我们的研究结果支持了一个模型，其中在透镜中GJIC的角度梯度，从而正确的透镜功能，是依赖于FGF和BMP途径之间的信号传导。
Homeostasis in the lens is dependent on an extensive network of cell-to-cell gap junctional channels. Gap junction-mediated intercellular coupling (GJIC) is higher in the equatorial region of the lens than at either pole, an asymmetry believed essential for lens transparency. Primary cultures of embryonic chick lens epithelial cells up-regulate GJIC in response to purified fibroblast growth factor (FGF) 1/2 or to medium conditioned by vitreous bodies, the major reservoir of factors (including FGF) for the lens equator. We show that purified bone morphogenetic protein (BMP) 2, -4, and -7 also up-regulate GJIC in these cultures. BMP2, -4, or both are present in vitreous body conditioned medium, and BMP4 and -7 are endogenously expressed by lens cells. Remarkably, lens-derived BMP signaling is required for up-regulation of GJIC by purified FGF, and sufficient for up-regulation by vitreous humor. This is the first demonstration of an obligatory interaction between FGF and BMPs in postplacode lens cells, and of a role for FGF/BMP cross-talk in regulating GJIC in any cell type. Our results support a model in which the angular gradient in GJIC in the lens, and thus proper lens function, is dependent on signaling between the FGF and BMP pathways.