The serpin PN1 is a feedback regulator of FGF signaling in germ layer and primary axis formation
The serpin PN1 is a feedback regulator of FGF signaling in germ layer and primary axis formation
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DOI：
10.1242/dev.113886
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发表时间：
2015-03-15
期刊：
影响因子：
4.6
通讯作者：
Pera, Edgar M.
中科院分区：
文献类型：
--
作者：
Acosta, Helena;Iliev, Dobromir;Pera, Edgar M.
胚层形成和主轴发育依赖于成纤维细胞生长因子（FGF）。在非洲爪蟾中，分泌的丝氨酸蛋白酶HtrA 1通过促进FGF信号的传播诱导中胚层和后部躯干/尾部结构。在这里，我们表明，丝氨酸蛋白酶抑制剂蛋白酶连接蛋白-1（PN 1）是转录激活的FGF信号，抑制中胚层和促进头部发育的mRNA注射胚胎。针对PN 1的反义吗啉代寡核苷酸具有相反的作用并抑制外胚层命运。然而，外胚层和前头部结构可以恢复PN 1耗尽胚胎时，HtrA 1和FGF受体的活动减少，表明FGF信号负调控它们的形成。我们发现，PN 1结合并抑制HtrA 1，防止蛋白聚糖Syndecan 4的降解，并限制旁分泌FGF/ERK信号传导。我们的数据表明，PN 1是FGF信号的负反馈调节器，在外胚层和头部发育中具有重要作用。
Germ layer formation and primary axis development rely on Fibroblast growth factors (FGFs). In Xenopus, the secreted serine protease HtrA1 induces mesoderm and posterior trunk/tail structures by facilitating the spread of FGF signals. Here, we show that the serpin Protease nexin-1 (PN1) is transcriptionally activated by FGF signals, suppresses mesoderm and promotes head development in mRNA-injected embryos. An antisense morpholino oligonucleotide against PN1 has the opposite effect and inhibits ectodermal fate. However, ectoderm and anterior head structures can be restored in PN1-depleted embryos when HtrA1 and FGF receptor activities are diminished, indicating that FGF signals negatively regulate their formation. We show that PN1 binds to and inhibits HtrA1, prevents degradation of the proteoglycan Syndecan 4 and restricts paracrine FGF/Erk signaling. Our data suggest that PN1 is a negative-feedback regulator of FGF signaling and has important roles in ectoderm and head development.