FGF signaling regulates otic placode induction and refinement by controlling both ectodermal target genes and hindbrain Wnt8a.
FGF signaling regulates otic placode induction and refinement by controlling both ectodermal target genes and hindbrain Wnt8a.
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DOI：
10.1016/j.ydbio.2010.02.016
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发表时间：
2010-04-15
影响因子：
2.7
通讯作者：
Mansour, Suzanne L.
中科院分区：
文献类型：
--
作者：
Urness, Lisa D.;Paxton, Christian N.;Wang, Xiaofen;Schoenwolf, Gary C.;Mansour, Suzanne L.
内耳上皮细胞，具有听觉和平衡所必需的感觉、非感觉和神经元细胞类型的复杂阵列，来源于称为耳基板的头部外胚层的增厚片。缺乏Fgf 3和Fgf 10的小鼠胚胎不能启动内耳发育，因为在耳前区域内不能指定适当的基因表达模式。为了理解启动内耳发育的转录“蓝图”，我们使用微阵列分析来鉴定在对照和Fgf 3-/-; Fgf 10-/-胚胎中差异表达的预期基板基因。通过原位杂交验证了下调类中的几个基因，包括Hmx 3，Hmx 2，Foxg 1，Sox 9，Has 2和Slc 26 a9。我们还分析了其他耳诱导研究中提出的候选靶基因。两个基板标志物Fgf 4和Foxi 3在Fgf 3-/-; Fgf 10-/-胚胎中下调，而颅表皮标志物Foxi 2在双突变体中扩增，类似于其在耳基板中阻断WNT反应时的行为。对后脑Wnt基因的分析显示，在FGF缺陷的胚胎中只有Wnt 8a减少或缺失，甚至一些Fgf 3-/-、Fgf 10-/+和Fgf 3-/-胚胎也不能表达Wnt 8a，这表明Fgf 3在Wnt 8a表达中起关键作用，而Fgf 10在Wnt 8a表达中起次要作用。鸡外植体测定显示，FGF 3或FGF 4，而不是FGF 10，足以诱导Wnt 8a。总的来说，我们的研究结果表明，Wnt 8a提供了FGF诱导的耳前区的形成和耳基板到邻近后脑的外胚层的限制之间的联系。
The inner ear epithelium, with its complex array of sensory, non-sensory, and neuronal cell types necessary for hearing and balance, is derived from a thickened patch of head ectoderm called the otic placode. Mouse embryos lacking both Fgf3 and Fgf10 fail to initiate inner ear development because appropriate patterns of gene expression fail to be specified within the pre-otic field. To understand the transcriptional “blueprint” initiating inner ear development, we used microarray analysis to identify prospective placode genes that were differentially expressed in control and Fgf3-/-;Fgf10-/- embryos. Several genes in the down-regulated class, including Hmx3, Hmx2, Foxg1, Sox9, Has2, and Slc26a9 were validated by in situ hybridization. We also assayed candidate target genes suggested by other studies of otic induction. Two placode markers, Fgf4 and Foxi3, were down-regulated in Fgf3-/-;Fgf10-/- embryos, whereas Foxi2, a cranial epidermis marker, was expanded in double mutants, similar to its behavior when WNT responses are blocked in the otic placode. Assays of hindbrain Wnt genes revealed that only Wnt8a was reduced or absent in FGF-deficient embryos, and that even some Fgf3-/-;Fgf10-/+ and Fgf3-/- embryos failed to express Wnt8a, suggesting a key role for Fgf3, and a secondary role for Fgf10, in Wnt8a expression. Chick explant assays showed that FGF3 or FGF4, but not FGF10, were sufficient to induce Wnt8a. Collectively, our results suggest that Wnt8a provides the link between FGF-induced formation of the pre-otic field and restriction of the otic placode to ectoderm adjacent to the hindbrain.
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影响因子：
4.6
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通讯作者：
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