Fgf and Hh signalling act on a symmetrical pre-pattern to specify anterior and posterior identity in the zebrafish otic placode and vesicle

Fgf and Hh signalling act on a symmetrical pre-pattern to specify anterior and posterior identity in the zebrafish otic placode and vesicle
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DOI:
10.1242/dev.066639
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发表时间:
2011-09-15
期刊:
影响因子:
4.6
通讯作者:
Whitfield, Tanya T.
Whitfield, Tanya T.
中科院分区:
生物学2区
文献类型:
--
作者:
Hammond, Katherine L.;Whitfield, Tanya T.

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耳前后轴的特化是内耳发育过程中最早的模式化事件之一。在斑马鱼,刺猬信号是必要的,足以指定后耳的身份之间的10体节(耳基板)和20体节(早期耳囊)阶段。我们现在表明,成纤维细胞生长因子信号是必要的和足够的前耳规格在一个类似的时期,一个功能,是完全分离的早期作用,耳基板诱导。在lia(-/-)(fgf 3(-/-))突变体中,前耳特征减少,但不会完全丧失。然而,使用pan-Fgf抑制剂SU 5402阻断10-20体节处的所有Fgf信号传导导致前部耳结构的丧失和后部区域的镜像复制。相反,在类似的时期,使用热休克诱导型转基因株系过量表达fgf 3,导致后耳结构的丧失和前耳结构域的重复。这些表型与Hedgehog信号传导改变时观察到的表型相反。在10和20体节之间的FGF和Hedgehog功能的损失导致对称的耳囊,既没有前部也没有后部的身份,然而,在耳朵的前端和后端保留限定的极。这些数据表明,FGF和刺猬作用于对称的耳前模式,以指定前耳和后耳的身份,分别。每个信号通路都具有指导性的活动:两者都不能简单地抑制另一个信号通路的活动,而且,它们似乎是斑马鱼耳朵前后不对称的关键参与者。
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.