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首页> 美国卫生研究院文献>Frontiers in Genetics >FGF Gradient Controls Boundary Position Between Proliferating and Differentiating Cells and Regulates Lacrimal Gland Growth Dynamics
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FGF Gradient Controls Boundary Position Between Proliferating and Differentiating Cells and Regulates Lacrimal Gland Growth Dynamics

机译：FGF梯度控制增殖和分化细胞之间的边界位置，并调节泪腺生长动力学。

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Fibroblast growth factor (FGF) signaling plays an important role in controlling cell proliferation, survival, and cell movements during branching morphogenesis of many organs. In mammals branching morphogenesis is primarily regulated by members of the FGF7-subfamily (FGF7 and FGF10), which are expressed in the mesenchyme, and signal to the epithelial cells through the “b” isoform of fibroblast growth factor receptor-2 (FGFR2). Our previous work demonstrated that FGF7 and FGF10 form different gradients in the extracellular matrix (ECM) and induce distinct cellular responses and gene expression profiles in the lacrimal and submandibular glands. The last finding was the most surprising since both FGF7 and FGF10 bind signal most strongly through the same fibroblast growth factor receptor-2b isoform (FGFR2b). Here we revisit this question to gain an explanation of how the different FGFs regulate gene expression. For this purpose, we employed our ex vivo epithelial explant migration assay in which isolated epithelial explants are grown near the FGF loaded beads. We demonstrate that the graded distribution of FGF induces activation of ERK1/2 MAP kinases that define the position of the boundary between proliferating “bud” and differentiating “stalk” cells of growing lacrimal gland epithelium. Moreover, we showed that gene expression profiles of the epithelial explants exposed to distinct FGFs strictly depend on the ratio between “bud” and “stalk” area. Our data also suggests that differentiation of “stalk” and “bud” regions within the epithelial explants is necessary for directional and persistent epithelial migration. Gaining a better understanding of FGF functions is important for development of new approaches to enhance tissue regeneration.
机译：成纤维细胞生长因子（FGF）信号在许多器官分支形态发生过程中，在控制细胞增殖，存活和细胞运动中起着重要作用。在哺乳动物中，分支形态发生主要受在间充质中表达的FGF7亚家族成员（FGF7和FGF10）调控，并通过成纤维细胞生长因子受体2（FGFR2）的“ b”同工型信号传递至上皮细胞。我们以前的工作表明，FGF7和FGF10在细胞外基质（ECM）中形成不同的梯度，并在泪腺和下颌下腺中诱导出不同的细胞反应和基因表达谱。最后一个发现是最令人惊讶的，因为FGF7和FGF10都通过相同的成纤维细胞生长因子受体2b同种型（FGFR2b）最强地结合信号。在这里，我们重新审视这个问题，以解释不同的FGF如何调节基因表达。为此，我们采用了离体上皮外植体迁移试验，其中分离的上皮外植体生长在FGF负载珠附近。我们证明，FGF的分级分布诱导了ERK1 / 2 MAP激酶的激活，该激酶定义了正在生长的泪腺上皮的增殖“芽”和分化“茎”细胞之间的边界位置。此外，我们发现暴露于不同FGF的上皮外植体的基因表达谱严格取决于“芽”与“茎”面积之间的比率。我们的数据还表明，上皮外植体中“茎”和“芽”区域的区分对于方向性和持久性上皮迁移是必要的。更好地了解FGF功能对于开发增强组织再生的新方法至关重要。

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