Three-dimensional live imaging of Atoh1 reveals the dynamics of hair cell induction and organization in the developing cochlea
Three-dimensional live imaging of Atoh1 reveals the dynamics of hair cell induction and organization in the developing cochlea
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DOI：
10.1242/dev.177881
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发表时间：
2019-11-01
期刊：
影响因子：
4.6
通讯作者：
Kageyama, Ryoichiro
中科院分区：
文献类型：
--
作者：
Tateya, Tomoko;Sakamoto, Susumu;Kageyama, Ryoichiro
在耳蜗发育过程中，毛细胞（HC）和支持细胞在前感觉区分化形成Corti器官，但一排内毛细胞（IHC）和三排外毛细胞（OHC）的组织方式尚不清楚。在这里，我们研究了HC诱导的过程中，通过监测Atoh 1-EGFP基因敲入小鼠胚胎耳蜗外植体中Atoh 1的表达，并表明只有表达Atoh 1超过一定阈值的细胞才被选择用于HC命运测定。HC诱导最初发生在前感觉域的内侧边缘以形成IHC，随后在外侧边缘以形成OHC，而Hedgehog信号传导在IHC和OHC之间保持空间，导致Corti隧道的形成。这些结果揭示了HC命运控制中Atoh 1的动态表达，并表明多方向信号调节OHC诱导，从而组织Corti器官的原型。
During cochlear development, hair cells (HCs) and supporting cells differentiate in the prosensory domain to form the organ of Corti, but how one row of inner HCs (IHCs) and three rows of outer HCs (OHCs) are organized is not well understood. Here, we investigated the process of HC induction by monitoring Atoh1 expression in cochlear explants of Atoh1-EGFP knock-in mouse embryos and showed that only the cells that express Atoh1 over a certain threshold are selected for HC fate determination. HC induction initially occurs at the medial edge of the prosensory domain to form IHCs and subsequently at the lateral edge to form OHCs, while Hedgehog signaling maintains a space between IHCs and OHCs, leading to formation of the tunnel of Corti. These results reveal dynamic Atoh1 expression in HC fate control and suggest that multi-directional signals regulate OHC induction, thereby organizing the prototype of the organ of Corti.