Abstract：
Neural induction by cell-cell signaling was discovered a century ago by the organizer transplantations of Spemann and Mangold in amphibians. Spemann later found that early dorsal blastopore lips induced heads and late organizers trunk-tail structures. Identifying region-specific organizer signals has been a driving force in the progress of animal biology. Head induction in the absence of trunk is designated archencephalic differentiation. Two specific head inducers, Cerberus and Insulin-like growth factors (IGFs), that induce archencephalic brain but not trunk-tail structures have been described previously. However, whether these two signals interact with each other had not been studied to date and was the purpose of the present investigation. It was found that Cerberus, a multivalent growth factor antagonist that inhibits Nodal, BMP and Wnt signals, strongly cooperated with IGF2, a growth factor that provides a positive signal through tyrosine kinase IGF receptors that activate MAPK and other pathways. The ectopic archencephalic structures induced by the combination of Cerberus and IGF2 are of higher frequency and larger than either one alone. They contain brain, a cyclopic eye and multiple olfactory placodes, without trace of trunk structures such as notochord or somites. A dominant-negative secreted IGF receptor 1 blocked Cerberus activity, indicating that endogenous IGF signals are required for ectopic brain formation. In a sensitized embryonic system, in which embryos were depleted of β-catenin, IGF2 did not by itself induce neural tissue while in combination with Cerberus it greatly enhanced formation of circular brain structures expressing the anterior markers Otx2 and Rx2a, but not spinal cord or notochord markers. The main conclusion of this work is that IGF provides a positive signal initially uniformly expressed throughout the embryo that potentiates the effect of an organizer-specific negative signal mediated by Cerberus. The results are discussed in the context of the history of neural induction.
摘要：
一个世纪前，组织者在两栖动物中移植了Spemann和Mangold，发现了细胞-细胞信号传导的神经诱导。Spemann后来发现，早期的背泡孔嘴唇会引起头部和晚期组织者的躯干-尾巴结构。识别特定区域的组织者信号一直是动物生物学发展的驱动力。在没有躯干的情况下，头部诱导被称为前脑分化。两个特定的头部诱导器，Cerberus和胰岛素样生长因子（IGFs），先前已经描述了诱导脑前脑而不是躯干-尾巴结构。然而,这两种信号是否相互作用迄今尚未被研究，这是本次调查的目的。发现Cerberus,抑制Nodal的多价生长因子拮抗剂，BMP和Wnt信号,与IGF2强烈合作，IGF2是一种生长因子，通过激活MAPK和其他途径的酪氨酸激酶IGF受体提供阳性信号。Cerberus和IGF2联合诱导的异位脑结构比单独的任何一种都具有更高的频率和更大。它们包含大脑，环线眼和多个嗅觉斑，没有躯干结构的痕迹，如脊索或体节。显性阴性分泌的IGF受体1阻断了Cerberus的活性，表明内源性IGF信号是异位脑形成所必需的。在一个敏感的胚胎系统中，在胚胎中β-连环蛋白耗尽，IGF2本身并不诱导神经组织，而与Cerberus结合，它大大增强了表达前标记Otx2和Rx2a的圆形脑结构的形成。但不是脊髓或脊索标记。这项工作的主要结论是，IGF提供了最初在整个胚胎中均匀表达的阳性信号，从而增强了由Cerberus介导的组织者特异性阴性信号的作用。在神经诱导史的背景下讨论了结果。
