The acquisition of positional information across the radial axis of the cochlea.

Document Type

Article

Publication Date

3-2020

Keywords

JMG

JAX Source

Dev Dyn 2020 Mar; 249(3):281-297

Volume

249

Issue

3

First Page

281

Last Page

297

ISSN

1097-0177

PMID

31566832

DOI

https://doi.org/10.1002/dvdy.118

Grant

DC016376,The Jackson Laboratory Start Up Program

Abstract

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.

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