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碱性成纤维细胞生长因子作为非洲爪蟾中枢神经系统前后轴可能的形态发生素。

bFGF as a possible morphogen for the anteroposterior axis of the central nervous system in Xenopus.

作者信息

Kengaku M, Okamoto H

机构信息

Department of Neurobiology, Faculty of Medicine, University of Tokyo, Japan.

出版信息

Development. 1995 Sep;121(9):3121-30. doi: 10.1242/dev.121.9.3121.

Abstract

Vertebrate neural development is initiated during gastrulation by the inductive action of the dorsal mesoderm (Spemann's organizer in amphibians) on neighbouring ectoderm, which eventually gives rise to the central nervous system from forebrain to spinal cord. Here we present evidence that bFGF can mimic the organizer action by inducing Xenopus ectoderm cells in culture to express four position-specific neural markers (XeNK-2, En-2, XIHbox1 and XIHbox6) along the anteroposterior axis. bFGF also induced the expression of a general neural marker NCAM but not the expression of immediate-early mesoderm markers (goosecoid, noggin, Xbra and Xwnt-8), suggesting that bFGF directly neuralized ectoderm cells without forming mesodermal cells. The bFGF dose required to induce the position-specific markers was correlated with the anteroposterior location of their expression in vivo, with lower doses eliciting more anterior markers and higher doses more posterior markers. These data indicate that bFGF or its homologue is a promising candidate for a neural morphogen for anteroposterior patterning in Xenopus. Further, we showed that the ability of ectoderm cells to express the anterior markers in response to bFGF was lost by mid-gastrula, before the organizer mesoderm completely underlies the anterior dorsal ectoderm. Thus, an endogenous FGF-like molecule released from the involuting organizer may initiate the formation of the anteroposterior axis of the central nervous system during the early stages of gastrulation by forming a concentration gradient within the plane of dorsal ectoderm.

摘要

脊椎动物的神经发育在原肠胚形成过程中由背侧中胚层(两栖动物中的施佩曼组织者)对邻近外胚层的诱导作用启动,最终产生从前脑到脊髓的中枢神经系统。我们在此提供证据表明,碱性成纤维细胞生长因子(bFGF)可通过诱导培养中的非洲爪蟾外胚层细胞沿前后轴表达四种位置特异性神经标记物(XeNK-2、En-2、XIHbox1和XIHbox6)来模拟组织者的作用。bFGF还诱导了一种通用神经标记物神经细胞黏附分子(NCAM)的表达,但未诱导早期中胚层标记物(鹅膏蕈碱、头蛋白、Xbra和Xwnt-8)的表达,这表明bFGF直接使外胚层细胞神经化而不形成中胚层细胞。诱导位置特异性标记物所需的bFGF剂量与其在体内表达的前后位置相关,较低剂量引发更多前部标记物,较高剂量引发更多后部标记物。这些数据表明,bFGF或其同源物是非洲爪蟾前后模式形成的神经形态发生素的一个有前景的候选物。此外,我们表明,在原肠胚中期,在组织者中胚层完全位于前背侧外胚层下方之前,外胚层细胞响应bFGF表达前部标记物的能力丧失。因此,从内卷的组织者释放的内源性FGF样分子可能在原肠胚形成的早期阶段通过在背侧外胚层平面内形成浓度梯度来启动中枢神经系统前后轴的形成。

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