Essential role of BMPs in FGF-induced secondary lens fiber differentiation.
Essential role of BMPs in FGF-induced secondary lens fiber differentiation.
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DOI：
10.1016/j.ydbio.2008.09.003
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发表时间：
2008-12-15
影响因子：
2.7
通讯作者：
Musil, Linda S.
中科院分区：
文献类型：
--
作者：
Boswell, Bruce A.;Overbeek, Paul A.;Musil, Linda S.
广泛认为玻璃体液来源的FGF是前透镜上皮细胞分化为富含纤维堆积的纤维所必需的。我们表明，BMP 2，4和7可以诱导表达的原代透镜细胞培养物中的纤维分化的标记物的程度相当于FGF或培养基条件的完整的玻璃体（VEGF 3）。用noggin消除BMP 2/4/7信号传导抑制了VEGF 1上调纤维标记物表达。值得注意的是，头蛋白和抗BMP抗体也阻止了纯化的FGF（但不是无关的刺激）上调相同的纤维特异性蛋白。这种效应可归因于抑制由透镜细胞自身产生的BMP。虽然BMP信号传导是FGF增强纤维分化所必需的，但相反的情况并非如此。在转基因小鼠的晶状体中表达头蛋白导致出生后上皮细胞向次级纤维分化的阻滞，上皮细胞单层延伸到器官的后极。这些结果揭示了BMP在二次纤维形成中的核心重要性，并表明尽管FGF可能是该过程所必需的，但它是不够的。纤维细胞的分化，以及因此的正常视力，依赖于FGF和BMP信号通路之间的相互作用。
It is widely accepted that vitreous humor-derived FGFs are required for the differentiation of anterior lens epithelial cells into crystallin-rich fibers. We show that BMP 2, 4, and 7 can induce the expression of markers of fiber differentiation in primary lens cell cultures to an extent equivalent to FGF or medium conditioned by intact vitreous bodies (VBCM). Abolishing BMP 2/4/7 signaling with noggin inhibited VBCM from upregulating fiber marker expression. Remarkably, noggin and anti-BMP antibodies also prevented purified FGF (but not unrelated stimuli) from upregulating the same fiber-specific proteins. This effect is attributable to inhibition of BMPs produced by the lens cells themselves. Although BMP signaling is required for FGF to enhance fiber differentiation, the converse is not true. Expression of noggin in the lenses of transgenic mice resulted in a postnatal block of epithelial-to-secondary fiber differentiation, with extension of the epithelial monolayer to the posterior pole of the organ. These results reveal the central importance of BMP in secondary fiber formation and show that although FGF may be necessary for this process, it is not sufficient. Differentiation of fiber cells, and thus proper vision, is dependent on cross-talk between the FGF and BMP signaling pathways.
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作者：
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