Sprouty2 controls proliferation of palate mesenchymal cells via fibroblast growth factor signaling
Sprouty2 controls proliferation of palate mesenchymal cells via fibroblast growth factor signaling
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DOI：
10.1016/j.bbrc.2010.12.116
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发表时间：
2011-01-28
影响因子：
3.1
通讯作者：
Nakamura, Seiji
中科院分区：
文献类型：
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作者：
Matsumura, Kaori;Taketomi, Takaharu;Nakamura, Seiji
腭裂是最常见的颅面畸形之一。成纤维细胞生长因子 (FGF) 在腭发育过程中相邻组织之间的相互作用中发挥着核心作用，并且 FGF 信号通路已被证明受到 Sprouty 蛋白家族成员的抑制。在这项研究中，我们报告了 Sprouty2 缺陷 (KO) 小鼠腭裂的发生率，这可能是由于腭架抬高失败引起的。 Sprouty2 缺陷的腭在腭器官培养中完全融合。然而，通过 Ki-67 染色估计，与 WT 小鼠相比，Sprouty2 KO 小鼠的腭间充质细胞增殖有所增加。与 WT 对照相比，Sprouty2 缺失的上颚表达更高水平的 FGF 靶基因，例如 Msx1、Etv5 和 Ptx1。此外，在用 Sprouty2 小干扰 RNA 转染的腭间充质细胞中，增殖和响应 FGF 的细胞外信号调节激酶 (Erk) 激活得到增强。这些结果表明 Sprouty2 通过 FGF 信号传导调节腭间充质细胞增殖，并参与腭架抬高。 (C) 2010 Elsevier Inc. 保留所有权利。
Cleft palate is one of the most common craniofacial deformities. The fibroblast growth factor (FGF) plays a central role in reciprocal interactions between adjacent tissues during palatal development, and the FGF signaling pathway has been shown to be inhibited by members of the Sprouty protein family. In this study, we report the incidence of cleft palate, possibly caused by failure of palatal shelf elevation, in Sprouty2-deficient (KO) mice. Sprouty2-deficient palates fused completely in palatal organ culture. However, palate mesenchymal cell proliferation estimated by Ki-67 staining was increased in Sprouty2 KO mice compared with WT mice. Sprouty2-null palates expressed higher levels of FGF target genes, such as Msx1, Etv5, and Ptx1 than WT controls. Furthermore, proliferation and the extracellular signal-regulated kinase (Erk) activation in response to FGF was enhanced in palate mesenchymal cells transfected with Sprouty2 small interfering RNA. These results suggest that Sprouty2 regulates palate mesenchymal cell proliferation via FGF signaling and is involved in palatal shelf elevation. (C) 2010 Elsevier Inc. All rights reserved.