Exogenous FGF-4 can suppress anterior development in the mouse embryo during neurulation and early organogenesis

Exogenous FGF-4 can suppress anterior development in the mouse embryo during neurulation and early organogenesis
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DOI:
10.1006/dbio.2000.9663
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发表时间:
2000-05-01
影响因子:
2.7
通讯作者:
Tam, PPL
Tam, PPL
中科院分区:
生物学3区
文献类型:
--
作者:
Davidson, BP;Cheng, L;Tam, PPL

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成纤维细胞生长因子 (FGF) 肽生长因子家族的成员在小鼠原肠胚形成和早期器官发生期间的胚层衍生物中广泛表达。我们研究了在原始条纹阶段胚胎中施用重组 FGF-4 的效果,以测试身体规划的模式是否可能受到该生长因子的影响。 EGF 处理后不久,胚胎组织上调了 Brachyury 和 RTK 信号调节因子 Spry2 的表达,表明 FGF 信号被激活,作为对外源 EGF 的立即反应。与此同时,Hesx1 的表达在胚胎的预期前部区域受到抑制。体外发育24小时后,胚胎表现出剂量相关的前脑形态发生抑制、中脑-后脑分区破坏以及胚胎中胚层分化抑制。总体而言,原肠胚晚期前后轴的发育对外源性 FGF-4 的递送敏感。与 Spry2 表达相关的早期反应表明,观察到的后期表型可能主要与 FGF 信号通路的抑制有关。 (C) 2000 年学术出版社。
Members of the fibroblast growth factor (FGF) family of peptide growth factors are widely expressed in the germ layer derivatives during gastrulation and early organogenesis of the mouse. We have investigated the effect of administering recombinant FGF-4 in the late-primitive streak stage embryo to test if the patterning of the body plan may be influenced by this growth factor. Shortly after EGF treatment the embryonic tissues up-regulated the expression of Brachyury and the RTK signaling regulator Spry2, suggesting that FGF signaling was activated as an immediate response to exogenous EGF. Concomitantly, Hesx1 expression was suppressed in the prospective anterior region of the embryo. After 24 h of in vitro development, embryos displayed a dosage-related suppression of forebrain morphogenesis, disruption of the midbrain-hindbrain partition, and inhibition of the differentiation of the embryonic mesoderm. Overall, development of the anterior-posterior axis in the late gastrula is sensitive to the delivery of exogenous FGF-4. The early response associated with the expression of Spry2 suggests that the later phenotype observed could be primarily related to an inhibition of the FGF signaling pathway. (C) 2000 Academic Press.