Stage-specific roles of FGF2 signaling in human neural development
Stage-specific roles of FGF2 signaling in human neural development
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DOI：
10.1016/j.scr.2016.08.012
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发表时间：
2016-09-01
影响因子：
1.2
通讯作者：
Sun, Yuh-Man
中科院分区：
文献类型：
--
作者：
Grabiec, Marta;Hribkova, Hana;Sun, Yuh-Man
本研究利用体外人胚胎干细胞发育模型阐明了FGF 2信号在神经发育过程中的阶段特异性作用。我们发现，在神经诱导开始之前，FGF 2信号的失调导致神经节（一种神经管样结构）的畸形，尽管细胞已经经历了神经诱导。ZO-1是一种极化的紧密连接蛋白，与FGF 2/FGFR 1共定位于神经突起的顶端区域，ZO-1的错位可能是导致神经发生异常的原因。此外，在神经再生阶段抑制FGF 2信号传导导致细胞增殖减少，细胞周期退出的细胞数量增加，以及过早的神经发生。这些作用可能是由NUMB介导的，在FGF 2信号传导抑制后，观察到NUMB的表达在神经突起的顶端区域富集，与PAX 6（+）/Ki 67（+）神经干细胞的消失和MAP 2（+）神经元的出现相一致。此外，我们的研究结果表明，hESC为基础的发育系统保留了类似的神经干细胞在体内的生态位。(C)2016年6月，作者。由Elsevier B. V.发布，这是CC BY许可下的开放获取文章。
This study elucidated the stage-specific roles of FGF2 signaling during neural development using in-vitro human embryonic stemcell-based developmental modeling. We found that the dysregulation of FGF2 signaling prior to the onset of neural induction resulted in the malformation of neural rosettes ( a neural tube-like structure), despite cells having undergone neural induction. The aberrant neural rosette formation may be attributed to the misplacement of ZO-1, which is a polarized tight junction protein and shown co-localized with FGF2/FGFR1 in the apical region of neural rosettes, subsequently led to abnormal neurogenesis. Moreover, the FGF2 signaling inhibition at the stage of neural rosettes caused a reduction in cell proliferation, an increase in numbers of cellswith cell-cycle exit, and premature neurogenesis. These effects may be mediated by NUMB, to which expression was observed enriched in the apical region of neural rosettes after FGF2 signaling inhibition coinciding with the disappearance of PAX6(+)/Ki67(+) neural stem cells and the emergence of MAP2(+) neurons. Moreover, our results suggested that the hESC-based developmental system reserved a similar neural stem cell niche in vivo. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license.