The mammalian cochlea detects sound and transmits this information to the brain. A cross section through the cochlea reveals functionally distinct epithelial domains arrayed around the circumference of a fluid-filled duct. Six major domains include two on the roof of the duct (Reissner's membrane medially and the stria vascularis laterally) and four across the floor of the duct, including the medial and lateral halves of the sensory domain, the organ of Corti. These radial domains are distinguishable in the embryonic cochlea by differential expression of transcription factors, and we focus here on a subset of the factors that can influence cochlear fates. We then move upstream of these genes to identify which of five signaling pathways (Notch, Fgf, Wnt, Bmp, and Shh) controls their spatial patterns of expression. We link the signaling pathways to their downstream genes, separating them by their radial position, to create putative gene regulatory networks (GRNs) from two time points, before and during the time when six radial compartments arise. These GRNs offer a framework for understanding the acquisition of positional information across the radial axis of the cochlea, and to guide therapeutic approaches to repair or regenerate distinct cochlear components that may contribute to hearing loss.

中文翻译：

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获取跨耳蜗径向轴的位置信息。

哺乳动物耳蜗检测声音并将此信息传输到大脑。穿过耳蜗的横截面显示功能不同的上皮结构域，排列在充满液体的导管周围。六个主要区域包括两个在导管顶部（内侧 Reissner 膜和外侧血管纹）和四个横跨导管底部，包括感觉域的内侧和外侧半部分，Corti 器官。这些径向结构域在胚胎耳蜗中可通过转录因子的差异表达进行区分，我们在这里重点讨论可以影响耳蜗命运的因素的一个子集。然后我们移动到这些基因的上游，以确定五种信号通路（Notch、Fgf、Wnt、Bmp 和 Shh）中的哪一种控制它们的空间表达模式。我们将信号通路连接到它们的下游基因，通过它们的径向位置将它们分开，从两个时间点创建假定的基因调控网络 (GRN)，在六个径向隔室出现之前和期间。这些 GRN 提供了一个框架，用于了解跨耳蜗径向轴的位置信息的获取，并指导治疗方法来修复或再生可能导致听力损失的不同耳蜗组件。