A gradient of Wnt activity positions the neurosensory domains of the inner ear.
A gradient of Wnt activity positions the neurosensory domains of the inner ear.
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DOI：
10.7554/elife.59540
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发表时间：
2021-03-11
期刊：
影响因子：
7.7
通讯作者：
Daudet N
中科院分区：
文献类型：
--
作者：
Żak M;Daudet N
内耳的听觉和前庭器官以及支配它们的神经元起源于在耳发育的早期阶段指定的Sox 2阳性和Notch活性神经感觉域。Sox 2最初存在于整个耳基板和耳囊，然后逐渐局限于腹内侧域。使用增益和功能丧失的方法在鸡耳囊，我们表明，这些早期的变化Sox 2表达的Wnt/β-连环蛋白信号以剂量依赖性的方式进行调节。高水平和非常低水平的Wnt活性都抑制Sox 2和神经感觉能力。然而，中间水平允许维持Sox 2表达和感觉器官形成。我们建议，背腹侧（高到低）的梯度和波的Wnt活动开始在耳基板的背侧边缘逐步限制Sox 2和Notch活动的腹侧的一半的耳囊，从而定位的neurosensory主管域在内耳。
The auditory and vestibular organs of the inner ear and the neurons that innervate them originate from Sox2-positive and Notch-active neurosensory domains specified at early stages of otic development. Sox2 is initially present throughout the otic placode and otocyst, and then it becomes progressively restricted to a ventro-medial domain. Using gain- and loss-of-function approaches in the chicken otocyst, we show that these early changes in Sox2 expression are regulated in a dose-dependent manner by Wnt/beta-catenin signalling. Both high and very low levels of Wnt activity repress Sox2 and neurosensory competence. However, intermediate levels allow the maintenance of Sox2 expression and sensory organ formation. We propose that a dorso-ventral (high-to-low) gradient and wave of Wnt activity initiated at the dorsal rim of the otic placode progressively restricts Sox2 and Notch activity to the ventral half of the otocyst, thereby positioning the neurosensory competent domains in the inner ear.