Distinct steps of neural induction revealed by Asterix, Obelix and TrkC, genes induced by different signals from the organizer.

Distinct steps of neural induction revealed by Asterix, Obelix and TrkC, genes induced by different signals from the organizer.
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DOI:
10.1371/journal.pone.0019157
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发表时间:
2011-04-29
期刊:
影响因子:
3.7
通讯作者:
Stern CD
Stern CD
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Pinho S;Simonsson PR;Trevers KE;Stower MJ;Sherlock WT;Khan M;Streit A;Sheng G;Stern CD

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当移植到宿主胚胎的外周区域时,羊膜组织器(Hensen淋巴结)可以诱导形成完整的神经系统。虽然BMP抑制与神经诱导有关,但非神经细胞不能对BMP拮抗剂产生反应,除非在使用BMP抑制剂之前至少暴露于移植物5小时。为了确定信号和节点信号前5小时的反应,进行了差异筛选。在这里,我们描述了三个早期反应基因:其中两个,Asterix和Obelix,编码以前未描述的功能未知的蛋白质,但Obelix似乎是一个核rna结合蛋白。第三种是TrkC,一种神经营养因子受体。这三种基因均可在4-5小时内被移植物诱导,但它们被FGF诱导的程度不同:FGF是诱导Asterix的必要条件和充分条件,诱导Obelix的充分条件但不是必要条件,诱导TrkC的充分条件和必要条件都不充分。这些基因也不会被视黄酸、Noggin、Chordin、Dkk1、Cerberus、HGF/SF、生长抑素或离子霉素介导的钙进入诱导。将这些基因的表达和调控与其他早期神经标记物进行比较,揭示了嫁接组织者神经诱导时基因表达的三个不同的“时代”或时间波,这反映在正常神经板发育的特定阶段。结果与神经诱导是由不同信号引起的级联反应一致,最终形成一个模式神经系统。
The amniote organizer (Hensen's node) can induce a complete nervous system when grafted into a peripheral region of a host embryo. Although BMP inhibition has been implicated in neural induction, non-neural cells cannot respond to BMP antagonists unless previously exposed to a node graft for at least 5 hours before BMP inhibitors. To define signals and responses during the first 5 hours of node signals, a differential screen was conducted. Here we describe three early response genes: two of them, Asterix and Obelix, encode previously undescribed proteins of unknown function but Obelix appears to be a nuclear RNA-binding protein. The third is TrkC, a neurotrophin receptor. All three genes are induced by a node graft within 4–5 hours but they differ in the extent to which they are inducible by FGF: FGF is both necessary and sufficient to induce Asterix, sufficient but not necessary to induce Obelix and neither sufficient nor necessary for induction of TrkC. These genes are also not induced by retinoic acid, Noggin, Chordin, Dkk1, Cerberus, HGF/SF, Somatostatin or ionomycin-mediated Calcium entry. Comparison of the expression and regulation of these genes with other early neural markers reveals three distinct “epochs”, or temporal waves, of gene expression accompanying neural induction by a grafted organizer, which are mirrored by specific stages of normal neural plate development. The results are consistent with neural induction being a cascade of responses elicited by different signals, culminating in the formation of a patterned nervous system.
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