Fzd3 Expression Within Inner Ear Afferent Neurons Is Necessary for Central Pathfinding.
Fzd3 Expression Within Inner Ear Afferent Neurons Is Necessary for Central Pathfinding.
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DOI：
10.3389/fnins.2021.779871
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发表时间：
2021
影响因子：
4.3
通讯作者：
Duncan JS
中科院分区：
文献类型：
--
作者：
Stoner ZA;Ketchum EM;Sheltz-Kempf S;Blinkiewicz PV;Elliott KL;Duncan JS
在发育过程中，内耳的传入神经元在后脑中做出精确的布线决定，反映了它们在周围的地形分布。这对于形成能够忠实处理听觉和前庭输入的感觉图至关重要。 Fzd3缺失小鼠内耳传入神经的混乱中央投射表明Wnt/PCP信号传导参与了这一过程，而非洲爪蟾的耳移植表明Fzd3在耳朵中是必要的，但在后脑中对于正确的传入导航不是必需的。然而，目前尚不清楚内耳 Fzd3 表达的哪种细胞类型正在影响内耳传入神经到达后脑中适当突触目标的引导。我们利用 Atoh1-cre 和 Neurod1-cre 小鼠系分别条件性敲除柯蒂氏器机械感觉毛细胞和内耳传入神经内的 Fzd3。在毛细胞内有条件地删除 Fzd3 后，内耳传入神经的中央拓扑分布得以维持，没有明显的形态缺陷。相比之下，内耳传入神经中 Fzd3 的条件性缺失会导致耳蜗和前庭传入神经的中枢寻路缺陷。在这里，我们表明 Fzd3 在内耳传入神经中以细胞自主方式发挥作用，调节后脑内的中枢寻路。
During development the afferent neurons of the inner ear make precise wiring decisions in the hindbrain reflective of their topographic distribution in the periphery. This is critical for the formation of sensory maps capable of faithfully processing both auditory and vestibular input. Disorganized central projections of inner ear afferents in Fzd3 null mice indicate Wnt/PCP signaling is involved in this process and ear transplantation in Xenopus indicates that Fzd3 is necessary in the ear but not the hindbrain for proper afferent navigation. However, it remains unclear in which cell type of the inner ear Fzd3 expression is influencing the guidance of inner ear afferents to their proper synaptic targets in the hindbrain. We utilized Atoh1-cre and Neurod1-cre mouse lines to conditionally knockout Fzd3 within the mechanosensory hair cells of the organ of Corti and within the inner ear afferents, respectively. Following conditional deletion of Fzd3 within the hair cells, the central topographic distribution of inner ear afferents was maintained with no gross morphological defects. In contrast, conditional deletion of Fzd3 within inner ear afferents leads to central pathfinding defects of both cochlear and vestibular afferents. Here, we show that Fzd3 is acting in a cell autonomous manner within inner ear afferents to regulate central pathfinding within the hindbrain.
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DOI：
10.1523/jneurosci.4508-10.2010
发表时间：
2010-11-24
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Fenstermaker AG;Prasad AA;Bechara A;Adolfs Y;Tissir F;Goffinet A;Zou Y;Pasterkamp RJ
通讯作者：
Pasterkamp RJ
影响因子：
4.6
作者：
Elliott, Karen L.;Fritzsch, Bernd
通讯作者：
Fritzsch, Bernd
影响因子：
4.6
作者：
Ghimire, Satish R.;Ratzan, Evan M.;Deans, Michael R.
通讯作者：
Deans, Michael R.
影响因子：
6.7
作者：
Appler JM;Goodrich LV
通讯作者：
Goodrich LV
影响因子：
1.2
作者：
Duncan, Jeremy;Kersigo, Jennifer;Fritzsch, Bernd
通讯作者：
Fritzsch, Bernd