Head organizer:Cerberus和IGF在爪蟾胚胎大脑诱导过程中的合作

IF 2.1 4区 生物学 Q3 DEVELOPMENTAL BIOLOGY
Yagmur Azbazdar, Edgar M Pera, Edward M De Robertis
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引用次数: 0

摘要

一个世纪前,斯佩曼(Spemann)和曼戈尔德(Mangold)通过两栖动物的组织器移植发现了细胞-细胞信号的神经诱导。斯佩曼后来发现,早期背侧胚泡唇诱导头部,晚期组织者诱导躯干-尾部结构。识别区域特异性组织者信号一直是动物生物学进步的推动力。在没有躯干的情况下诱导出头部被称为拱脑分化。两种特异性头部诱导因子 Cerberus 和胰岛素样生长因子 (Insulin-like growth factors, IGFs),可诱导头状脑分化,但不诱导躯干-尾部结构。然而,迄今为止,这两种信号是否相互影响尚未研究,这也是本次调查的目的。研究发现,Cerberus(一种抑制 Nodal、BMP 和 Wnt 信号的多价生长因子拮抗剂)与 IGF2(一种通过酪氨酸激酶 IGF 受体提供积极信号、激活 MAPK 和其他通路的生长因子)之间存在密切的合作关系。由 Cerberus 和 IGF2 共同诱导的异位拱脑结构比单独使用其中一种的频率更高、更大。它们包含大脑、环状眼和多个嗅胎座,但没有脊索或体节等躯干结构的痕迹。显性阴性分泌型 IGF 受体 1 阻断了 Cerberus 的活动,表明异位脑的形成需要内源性 IGF 信号。在一个去除了β-catenin的敏化胚胎系统中,IGF2本身并不能诱导神经组织的形成,而与Cerberus结合则能大大促进表达前部标记Otx2和Rx2a的环状脑结构的形成,但不能诱导脊髓或脊索标记的形成。这项工作的主要结论是,IGF 提供了一种最初在整个胚胎中均匀表达的积极信号,这种信号增强了由 Cerberus 介导的组织者特异性消极信号的效果。本文结合神经诱导的历史对这一结果进行了讨论。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Head organizer: Cerberus and IGF cooperate in brain induction in Xenopus embryos.

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.

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来源期刊
Cells & Development
Cells & Development DEVELOPMENTAL BIOLOGY-
CiteScore
3.70
自引率
0.00%
发文量
33
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