Sonic hedgehog antagonists reduce size and alter patterning of the frog inner ear.
Sonic hedgehog antagonists reduce size and alter patterning of the frog inner ear.
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DOI：
10.1002/dneu.22544
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发表时间：
2017-12
影响因子：
3
通讯作者：
Elliott KL
中科院分区：
文献类型：
--
作者：
Zarei S;Zarei K;Fritzsch B;Elliott KL
Sonic Hedgehog（Shh）信号在脊椎动物的发育中起着重要的作用，从增殖的调节到各种器官的形成。Shh影响内耳的背腹模式，但影响硬骨鱼的前后模式。目前，Shh在内耳发育中的功能仍不清楚，即在sarcopterygian/tetrapod谱系中的形态发生变化如何与耳朵中四肢和新听觉器官的进化相一致。在这项研究中，我们使用四足动物，非洲爪蟾，测试如何增加浓度的Shh信号通路拮抗剂，维莫德吉，影响耳朵的发展。维莫德吉治疗剂量依赖性地改变了耳、轴下肌的发育，并通过其与内耳传入神经的相互作用间接改变了Mauthner细胞的发育。总之，这些表型对逃避反应有影响。改变的Mauthner细胞可能有助于增加对刺激的反应时间。此外，躯干中轴下肌的增加可能有助于动物C起始屈曲角的细微变化。在耳中，随着维莫德吉浓度的增加，维莫德吉处理导致重力感觉上皮细胞之间的分离减少。此外，在较高剂量下，水平通道丢失，但没有对映体转化，如在缺乏Shh的硬骨鱼中。像在黑猩猩，Shh信号在青蛙影响背腹图案的耳朵，这表明，听觉感官的进化在sarcoprophians/四足动物进化的Shh轴规格的耳朵的转变。
Sonic Hedgehog (Shh) signaling plays a major role in vertebrate development, from regulation of proliferation to the patterning of various organs. In amniotes, Shh affects dorsoventral patterning in the inner ear but affects anteroposterior patterning in teleosts. Currently, it remains unknown the function of Shh in inner ear development in terms of how morphogenesis changes in the sarcopterygian/tetrapod lineage coincide with the evolution of limbs and novel auditory organs in the ear. In this study we used the tetrapod, Xenopus laevis, to test how increasing concentrations of the Shh signal pathway antagonist, Vismodegib, affects ear development. Vismodegib treatment dose dependently alters the development of the ear, hypaxial muscle, and indirectly the Mauthner cell through its interaction with the inner ear afferents. Together, these phenotypes have an effect on escape response. The altered Mauthner cell likely contributes to the increased time to respond to a stimulus. In addition, the increased hypaxial muscle in the trunk likely contributes to the subtle change in animal C-start flexion angle. In the ear, Vismodegib treatment results in decreasing segregation between the gravistatic sensory epithelia as the concentration of Vismodegib increases. Furthermore, at higher doses, there is a loss of the horizontal canal but no enantiomorphic transformation, as in bony fish lacking Shh. Like in amniotes, Shh signaling in frogs affects dorsoventral patterning in the ear, suggesting that auditory sensory evolution in sarcopterygians/tetrapods evolved with a shift of Shh axis specification of the ear.
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影响因子：
1
作者：
FRITZSCH, B;WAKE, MH
通讯作者：
WAKE, MH
影响因子：
64.8
作者：
FRITZSCH, B
通讯作者：
FRITZSCH, B
DOI：
10.1002/neu.10098
发表时间：
2002-11-05
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
Fritzsch, B;Beisel, KW;Reichardt, LF
通讯作者：
Reichardt, LF
影响因子：
64.5
作者：
Charron, F;Stein, E;Tessier-Lavigne, M
通讯作者：
Tessier-Lavigne, M
影响因子：
64.5
作者：
ERICSON, J;MUHR, J;EDLUND, T
通讯作者：
EDLUND, T