Morgan R, Sargent M G
Division of Developmental Biology, National Institute for Medical Research, Mill Hill, London, UK.
Development. 1997 Jul;124(14):2751-60. doi: 10.1242/dev.124.14.2751.
Expression of the RNA-helicase translation initiation factor, eIF4AII, in animal cap explants of Xenopus specifically upregulates genes expressed early in the neural plate border such as Xsna, Xslu, Pax-3 and XANF and also the cement gland marker XCG-1. eIF4AII is expressed specifically in the prospective neurectoderm from stage 11.5 and appears to have a significant role in mediating early patterning of the neurectoderm. It is induced by all known neural inducing regimes including secreted factors such as noggin, follistatin and chordin, transcription factors such as XlPou-2 and constructs that overcome repression of neural induction (tBMP-4R, lim-m3 and Xbra delta 304). It is also upregulated when neurulization occurs in embryonic ectoderm that has been disaggregated and reaggregated. While high amounts of injected mRNA of the neural inducers noggin, tBMP-4R and Xlpou-2 downregulate Xslu and upregulate the neural plate NCAM, smaller amounts of these mRNAs activate expression of eIF4AII and Xslu and suppress expression of epidermal keratin in animal cap assays. Ectopic expression of eIF4AII mRNA also upregulates transcription of the PKC alpha and beta genes. The sensitivity of the upregulation of neurectodermal markers to GF109203X indicates that the activity of a calcium activated protein kinase C (PKC) is also required. Furthermore ectopic expression of mouse eIF4AII mRNA upregulates the endogenous eIF4AII gene by a process that requires the activity of PKC. The effects of eIF4AII appear to be direct as conditional expression of eIF4AII in animal cap explants at the equivalent of stage 11.5 induces the endogenous eIF4AII and neural fold genes within 40 minutes. Expression of eIF4AII and activation of PKC sensitizes the embryonic ectoderm to the neuralising effect of noggin. We suggest that in developing embryos the neuralizing signal emanating from the organiser at first induces eIF4AII and the prospective neural crest in an arc low on the dorsal aspect of the embryo. As the neuralizing signal increases in intensity close to the organizer region, the tissue becomes committed to a neural plate phenotype. Expression of Xash-3A may suppress further expression of neural plate border genes within the prospective neural plate thereby subdividing the neurectoderm into two distinct regions.
RNA解旋酶翻译起始因子eIF4AII在非洲爪蟾动物帽外植体中的表达，特异性地上调了神经板边缘早期表达的基因，如Xsna、Xslu、Pax - 3和XANF，以及表皮腺标记物XCG - 1。eIF4AII从第11.5期开始在预期的神经外胚层中特异性表达，并且似乎在介导神经外胚层的早期模式形成中发挥重要作用。它可被所有已知的神经诱导机制诱导，包括分泌因子如头蛋白、卵泡抑素和脊索蛋白，转录因子如XlPou - 2以及克服神经诱导抑制的构建体（tBMP - 4R、lim - m3和Xbra delta 304）。当在已解离并重新聚集的胚胎外胚层中发生神经胚形成时，它也会上调。虽然大量注射神经诱导剂头蛋白、tBMP - 4R和Xlpou - 2的mRNA会下调Xslu并上调神经板NCAM，但在动物帽实验中，较少量的这些mRNA会激活eIF4AII和Xslu的表达并抑制表皮角蛋白的表达。eIF4AII mRNA的异位表达也会上调PKCα和β基因的转录。神经外胚层标记物上调对GF109203X的敏感性表明，钙激活蛋白激酶C（PKC）的活性也是必需的。此外，小鼠eIF4AII mRNA的异位表达通过一个需要PKC活性的过程上调内源性eIF4AII基因。eIF4AII的作用似乎是直接的，因为在相当于第11.5期的动物帽外植体中条件性表达eIF4AII会在40分钟内诱导内源性eIF4AII和神经褶基因。eIF4AII的表达和PKC的激活使胚胎外胚层对头蛋白的神经化作用敏感。我们认为，在发育中的胚胎中，来自组织者的神经化信号首先在胚胎背侧较低位置的弧中诱导eIF4AII和预期的神经嵴。随着靠近组织者区域的神经化信号强度增加，组织会确定为神经板表型。Xash - 3A的表达可能会抑制预期神经板内神经板边缘基因的进一步表达，从而将神经外胚层细分为两个不同的区域。
