MRC Centre for Developmental and Biomedical Genetics and Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, UK.
Development. 2011 Sep;138(18):3977-87. doi: 10.1242/dev.066639. Epub 2011 Aug 10.
Specification of the otic anteroposterior axis is one of the earliest patterning events during inner ear development. In zebrafish, Hedgehog signalling is necessary and sufficient to specify posterior otic identity between the 10 somite (otic placode) and 20 somite (early otic vesicle) stages. We now show that Fgf signalling is both necessary and sufficient for anterior otic specification during a similar period, a function that is completely separable from its earlier role in otic placode induction. In lia(-/-) (fgf3(-/-)) mutants, anterior otic character is reduced, but not lost altogether. Blocking all Fgf signalling at 10-20 somites, however, using the pan-Fgf inhibitor SU5402, results in the loss of anterior otic structures and a mirror image duplication of posterior regions. Conversely, overexpression of fgf3 during a similar period, using a heat-shock inducible transgenic line, results in the loss of posterior otic structures and a duplication of anterior domains. These phenotypes are opposite to those observed when Hedgehog signalling is altered. Loss of both Fgf and Hedgehog function between 10 and 20 somites results in symmetrical otic vesicles with neither anterior nor posterior identity, which, nevertheless, retain defined poles at the anterior and posterior ends of the ear. These data suggest that Fgf and Hedgehog act on a symmetrical otic pre-pattern to specify anterior and posterior otic identity, respectively. Each signalling pathway has instructive activity: neither acts simply to repress activity of the other, and, together, they appear to be key players in the specification of anteroposterior asymmetries in the zebrafish ear.
耳前-后轴的特化是内耳发育过程中最早的模式形成事件之一。在斑马鱼中，Hedgehog 信号通路对于在 10 体节（耳原基）和 20 体节（早期耳泡）阶段之间特化后耳的身份是必需且充分的。我们现在表明，Fgf 信号通路在类似的时期对于前耳的特化也是必需且充分的，其功能与它在耳原基诱导中的早期作用完全分离。在 lia(-/-)（fgf3(-/-)）突变体中，前耳特征减少，但并没有完全丧失。然而，在 10-20 体节使用泛 Fgf 抑制剂 SU5402 阻断所有 Fgf 信号通路，会导致前耳结构丢失和后区的镜像复制。相反，在类似时期使用热休克诱导的转基因系过表达 fgf3，会导致后耳结构丢失和前区的复制。这些表型与 Hedgehog 信号通路改变时观察到的相反。在 10 到 20 体节之间同时缺失 Fgf 和 Hedgehog 功能会导致没有前耳或后耳身份的对称耳泡，但它们仍然在前耳和后耳的前后两端保持明确的极。这些数据表明，Fgf 和 Hedgehog 作用于一个对称的耳前模式来分别特化前耳和后耳的身份。每个信号通路都具有指令活性：两者都不是简单地抑制对方的活性，而且，它们一起似乎是斑马鱼耳前-后不对称性特化的关键参与者。
