Sequential roles for Fgf4, En1 and Fgf8 in specification and regionalisation of the midbrain.
Sequential roles for Fgf4, En1 and Fgf8 in specification and regionalisation of the midbrain.
复制标题
DOI：
--
复制
发表时间：
1999-03
期刊：
影响因子：
4.6
通讯作者：
Huma Shamim;R. Mahmood;C. Logan;P. Doherty;A. Lumsden;I. Mason
中科院分区：
文献类型：
--
作者：
Huma Shamim;R. Mahmood;C. Logan;P. Doherty;A. Lumsden;I. Mason
涉及组织重组的实验表明，在中脑的规范和极化中，早期的垂直信号和后来的平面信号都存在。在这里，我们研究成纤维细胞生长因子在调节禽胚胎这些过程中的作用。我们发现，在检测到禽类胚胎中脑组织最早的分子标记En1转录本之前，Fgf4在Hensen’s结前脊索中表达。En1在体外神经板外植体中的表达需要脊索的存在，而FGF4模拟了脊索组织的这种作用。随后，成纤维细胞生长因子家族的第二个成员Fgf8在峡部表达，其表达方式与为发育中的中脑提供极化信号的方式一致。利用逆转录病毒载体外位表达En1，我们发现En1可以诱导Fgf8在中脑和后间脑表达。将FGF8蛋白引入前中脑或后间脑的结果与它至少是峡部活动的一部分是一致的，它可以使前组织重新极化，并将后者重新指定为中脑的命运。然而，FGF8能够诱导比FGF8本身更早开始表达的基因En1和Pax2的表达，这强烈表明FGF8的正常功能是维持后中脑的基因表达模式。最后，我们提供证据表明FGF8在鸟类中脑发育过程中也提供有丝分裂刺激。
Experiments involving tissue recombinations have implicated both early vertical and later planar signals in the specification and polarisation of the midbrain. Here we investigate the role of fibroblast growth factors in regulating these processes in the avian embryo. We show that Fgf4 is expressed in the notochord anterior to Hensen's node before transcripts for the earliest molecular marker of midbrain tissue in the avian embryo, En1, are detected. The presence of notochord is required for the expression of En1 in neural plate explants in vitro and FGF4 mimics this effect of notochord tissue. Subsequently, a second member of the fibroblast growth factor family, Fgf8, is expressed in the isthmus in a manner consistent with it providing a polarising signal for the developing midbrain. Using a retroviral vector to express En1 ectopically, we show that En1 can induce Fgf8 expression in midbrain and posterior diencephalon. Results of the introduction of FGF8 protein into the anterior midbrain or posterior diencephalon are consistent with it being at least part of the isthmic activity which can repolarise the former tissue and respecify the latter to a midbrain fate. However, the ability of FGF8 to induce expression of genes which have earlier onsets of expression than Fgf8 itself, namely En1 and Pax2, strongly suggests that the normal function of FGF8 is in maintaining patterns of gene expression in posterior midbrain. Finally, we provide evidence that FGF8 also provides mitogenic stimulation during avian midbrain development.