Fgf-dependent otic induction requires competence provided by FoxiI and Dlx3b
Fgf-dependent otic induction requires competence provided by FoxiI and Dlx3b
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DOI：
10.1186/1471-213x-7-5
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发表时间：
2007-01-19
影响因子：
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通讯作者：
Westerfield, Monte
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文献类型：
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作者：
Hans, Stefan;Christison, Joe;Westerfield, Monte
背景资料：内耳起源于一组专门的细胞，耳基板，形成于邻近后脑的神经板的侧边缘。以前的研究表明，成纤维细胞生长因子（FGFs）是耳诱导所必需的;在斑马鱼中，FGF 3和FGF 8的缺失导致耳组织的完全消融。此外，功能获得性研究表明，FGF信号传导不仅是必要的，但也足以耳诱导，虽然量的诱导异位耳组织后报告的fgf 3或fgf 8的错误表达不同的研究。我们先前提出，foxiI和dlx 3b可能提供形成耳的能力，因为foxiI和dlx 3b两者的缺失导致所有耳组织的消融，即使在存在全功能FGF信号传导通路的情况下。使用一个转基因株系，它允许我们在斑马鱼温度诱导型hsp 70启动子的控制下错误表达fgf 8，我们重新讨论了在基板诱导过程中FGF信号传导和耳功能的作用。我们发现fgf 8的错误表达不能诱导内源性耳野外异位耳泡的形成，并根据发育阶段产生不同的后果。fgf 8从1-细胞到中原肠胚阶段的过度表达分别导致无耳泡或小耳泡的形成。在这些阶段fgf 8的过表达从来没有导致foxiI或dlx 3b的异位表达，与以前的研究表明foxiI是由FGF信号激活。与我们的研究结果一致，我们发现Fgf信号传导的药理学抑制对foxiI或dlx 3b表达没有影响，相反，BMP信号传导直接激活foxiI，间接激活dlx 3b。与fgf 8的早期激活相反，fgf 8在原肠胚形成结束时过度表达，此时耳诱导开始，导致更大的耳泡。我们进一步表明，应用低剂量的视黄酸，不扰乱图案的前神经板导致扩大foxiI和大量的FGF依赖的耳induction.Conclusion：这些结果提供了进一步支持的假设，即foxiI和Dlx 3b提供能力的细胞响应FGF，形成一个耳基板。
Background: The inner ear arises from a specialized set of cells, the otic placode, that forms at the lateral edge of the neural plate adjacent to the hindbrain. Previous studies indicated that fibroblast growth factors (Fgfs) are required for otic induction; in zebrafish, loss of both Fgf3 and Fgf8 results in total ablation of otic tissue. Furthermore, gain-of-function studies suggested that Fgf signaling is not only necessary but also sufficient for otic induction, although the amount of induced ectopic otic tissue reported after misexpression of fgf3 or fgf8 varies among different studies. We previously suggested that FoxiI and Dlx3b may provide competence to form the ear because loss of both foxiI and dlx3b results in ablation of all otic tissue even in the presence of a fully functional Fgf signaling pathway.Results: Using a transgenic line that allows us to misexpress fgf8 under the control of the zebrafish temperature-inducible hsp70 promoter, we readdressed the role of Fgf signaling and otic competence during placode induction. We find that misexpression of fgf8 fails to induce formation of ectopic otic vesicles outside of the endogenous ear field and has different consequences depending upon the developmental stage. Overexpression of fgf8 from 1-cell to midgastrula stages leads to formation of no or small otic vesicles, respectively. Overexpression of fgf8 at these stages never leads to ectopic expression of foxiI or dlx3b, contrary to previous studies that indicated that foxiI is activated by Fgf signaling. Consistent with our results we find that pharmacological inhibition of Fgf signaling has no effect on foxiI or dlx3b expression, but instead, Bmp signaling activates foxiI, directly and dlx3b, indirectly. In contrast to early activation of fgf8, fgf8 overexpression at the end of gastrulation, when otic induction begins, leads to much larger otic vesicles. We further show that application of a low dose of retinoic acid that does not perturb patterning of the anterior neural plate leads to expansion of foxiI and to a massive Fgf-dependent otic induction.Conclusion: These results provide further support for the hypothesis that FoxiI and Dlx3b provide competence for cells to respond to Fgf and form an otic placode.