An inducible system for the study of FGF signalling in early amphibian development

An inducible system for the study of FGF signalling in early amphibian development
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DOI:
10.1016/s0012-1606(02)00120-3
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发表时间:
2003-04-01
影响因子:
2.7
通讯作者:
Isaacs, HV
Isaacs, HV
中科院分区:
生物学3区
文献类型:
--
作者:
Pownall, ME;Welm, BE;Isaacs, HV

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据报道,一种新型诱导型 FGF 信号系统在非洲爪蟾 (Xenopus laevis) 中的应用。我们证明,亲脂性合成二聚剂 AP20187 能够通过爪蟾胚胎中异位表达的 FGFR1 (iFGFR1) 突变体快速激活信号传导。 iFGFR1 缺乏胞外配体结合域,并包含与小鼠 FGFR1 胞内域融合的 AP20187 结合域。 AP20187 诱导信号传导至少在早期神经胚阶段是可能的,并且我们证明异位表达的 iFGFR1 蛋白持续到晚期神经胚阶段。我们发现,通过 iFGFR1 激活信号可以模拟许多先前报道的 FGF 活性,包括中胚层诱导、前部发育抑制和神经后化。我们表明,通过 FGF 信号传导对前后轴进行形态学后置的能力仅延伸到大约 10.5 阶段。我们证明,神经组织响应 FGF 信号而表达后标记 Hoxa7 和 Xcad3 的能力在原肠胚阶段结束时丧失。我们还表明,FGF 信号的激活会刺激神经组织的形态发生运动,至少直到原肠胚阶段结束。 (C) 2003 年爱思唯尔科学(美国)。版权所有。
The use of a novel inducible FGF signalling system in the frog Xenopus laevis is reported. We show that the lipophilic, synthetic, dimerizing agent AP20187 is able to rapidly activate signalling through an ectopically expressed mutant form of FGFR1 (iFGFR1) in Xenopus embryos. iFGFR1 lacks an extracellular ligand binding domain and contains an AP20187 binding domain fused to the intracellular domain of mouse FGFR1. Induction of signalling by AP20187 is possible until at least early neurula stages, and we demonstrate that ectopically expressed iFGFR1 protein persists until late neurula stages. We show that activation of signalling through iFGFR1 can mimic a number of previously reported FGF activities, including mesoderm induction, repression of anterior development, and neural posteriorization. We show that competence to morphological posteriorization of the anteroposterior axis by FGF signalling only extends until about stage 10.5. We demonstrate that the competence of neural tissue to express the posterior markers Hoxa7 and Xcad3, in response to FGF signalling, is lost by the end of gastrula stages. We also show that activation of FGF signalling stimulates morphogenetic movements in neural tissue until at least the end of the gastrula stage. (C) 2003 Elsevier Science (USA). All rights reserved.