FGF signalling through RAS/MAPK and PI3K pathways regulates cell movement and gene expression in the chicken primitive streak without affecting E-cadherin expression.
FGF signalling through RAS/MAPK and PI3K pathways regulates cell movement and gene expression in the chicken primitive streak without affecting E-cadherin expression.
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DOI：
10.1186/1471-213x-11-20
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发表时间：
2011-03-21
影响因子：
--
通讯作者：
Antin PB
中科院分区：
文献类型：
--
作者：
Hardy KM;Yatskievych TA;Konieczka J;Bobbs AS;Antin PB
FGF 信号传导调节早期胚胎发育的许多方面。在羊膜动物原肠胚形成过程中，外胚层细胞在原条中经历上皮间质转化（EMT），形成中胚层和内胚层。在缺乏 FGFR1 的小鼠中，原条中的外胚层细胞无法下调 E-钙粘蛋白并经历 EMT，并且细胞迁移受到抑制。本研究调查了 FGF 信号如何调节鸡胚胎原条中的细胞运动和基因表达。我们发现，药物抑制 FGFR 活性可阻止细胞通过鸡胚原条的迁移，而 E-钙粘蛋白的水平或细胞内定位没有明显改变。 E-钙粘蛋白定位于外胚层、原条和一些中胚层细胞的外围。 FGFR抑制导致邻近原条的前内胚层、原条和新形成的中胚层中大量调节基因的下调。这包括 FGF、NOTCH、EPH、PDGF 以及规范和非规范 WNT 途径的成员、这些途径的负调节因子以及大量转录调节基因。原条和中胚层中的 SNAI2 表达不会因 FGFR 抑制而改变，但仅在前移外胚层区域下调，对 E-钙粘蛋白没有显着影响。此外，SNAIL 的过度表达对 E-钙粘蛋白水平或外胚层、原条或中胚层细胞中的定位没有明显影响。 FGFR 活性调节不同的下游途径，包括 RAS/MAPK 和 PI3K/AKT。 MEK 或 AKT 的药理学抑制表明这些下游效应子在原肠胚形成过程中控制离散和重叠的基因组。 FGFR 活性调节已知细胞通过条纹或中胚层迁移所需的多种途径的成分，包括 RHOA、非经典 WNT 途径、PDGF 信号传导和细胞粘附蛋白 N-钙粘蛋白。在鸡胚胎中，FGF 信号传导通过似乎独立于 E-钙粘蛋白表达或蛋白质定位变化的机制来调节细胞通过原条的运动。 FGF 信号传导的药理学抑制对大组基因（包括主要信号传导途径和转录因子家族）产生的积极和消极影响表明 FGF 途径是鸡原肠胚形成过程中的调节焦点。
FGF signalling regulates numerous aspects of early embryo development. During gastrulation in amniotes, epiblast cells undergo an epithelial to mesenchymal transition (EMT) in the primitive streak to form the mesoderm and endoderm. In mice lacking FGFR1, epiblast cells in the primitive streak fail to downregulate E-cadherin and undergo EMT, and cell migration is inhibited. This study investigated how FGF signalling regulates cell movement and gene expression in the primitive streak of chicken embryos. We find that pharmacological inhibition of FGFR activity blocks migration of cells through the primitive streak of chicken embryos without apparent alterations in the level or intracellular localization of E-cadherin. E-cadherin protein is localized to the periphery of epiblast, primitive streak and some mesodermal cells. FGFR inhibition leads to downregulation of a large number of regulatory genes in the preingression epiblast adjacent to the primitive streak, the primitive streak and the newly formed mesoderm. This includes members of the FGF, NOTCH, EPH, PDGF, and canonical and non-canonical WNT pathways, negative modulators of these pathways, and a large number of transcriptional regulatory genes. SNAI2 expression in the primitive streak and mesoderm is not altered by FGFR inhibition, but is downregulated only in the preingression epiblast region with no significant effect on E-cadherin. Furthermore, over expression of SNAIL has no discernable effect on E-cadherin protein levels or localization in epiblast, primitive streak or mesodermal cells. FGFR activity modulates distinct downstream pathways including RAS/MAPK and PI3K/AKT. Pharmacological inhibition of MEK or AKT indicate that these downstream effectors control discrete and overlapping groups of genes during gastrulation. FGFR activity regulates components of several pathways known to be required for cell migration through the streak or in the mesoderm, including RHOA, the non-canonical WNT pathway, PDGF signalling and the cell adhesion protein N-cadherin. In chicken embryos, FGF signalling regulates cell movement through the primitive streak by mechanisms that appear to be independent of changes in E-cadherin expression or protein localization. The positive and negative effects on large groups of genes by pharmacological inhibition of FGF signalling, including major signalling pathways and transcription factor families, indicates that the FGF pathway is a focal point of regulation during gastrulation in chicken.