Canonical Notch signaling plays an instructive role in auditory supporting cell development

Dean P. Campbell, Elena Chrysostomou, Angelika Doetzlhofer

Research output: Contribution to journalArticle

Abstract

The auditory sensory epithelium, composed of mechano-sensory hair cells (HCs) and highly specialized glial-like supporting cells (SCs), is critical for our ability to detect sound. SCs provide structural and functional support to HCs and play an essential role in cochlear development, homeostasis and repair. Despite their importance, however, surprisingly little is known about the molecular mechanisms guiding SC differentiation. Here, we provide evidence that in addition to its well-characterized inhibitory function, canonical Notch signaling plays a positive, instructive role in the differentiation of SCs. Using γ-secretase inhibitor DAPT to acutely block canonical Notch signaling, we identified a cohort of Notch-regulated SC-specific genes, with diverse functions in cell signaling, cell differentiation, neuronal innervation and synaptogenesis. We validated the newly identified Notch-regulated genes in vivo using genetic gain (Emx2Cre/+; Rosa26N1ICD/+) and loss-of-function approaches (Emx2Cre/+; Rosa26DnMAML1/+). Furthermore, we demonstrate that Notch over-activation in the differentiating murine cochlea (Emx2Cre/+; Rosa26N1ICD/+) actively promotes a SC-specific gene expression program. Finally, we show that outer SCs-so called Deiters' cells are selectively lost by prolonged reduction (Emx2Cre/+; Rosa26DnMAML1/+/+) or abolishment of canonical Notch signaling (Fgfr3-iCreER; Rbpj-), indicating a critical role for Notch signaling in Deiters' cell development.

Original languageEnglish (US)
Article number19484
JournalScientific Reports
Volume6
DOIs
StatePublished - Jan 20 2016

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Cell Differentiation
Cochlea
Amyloid Precursor Protein Secretases
Neuroglia
Genes
Homeostasis
Epithelium
Gene Expression

ASJC Scopus subject areas

  • General

Cite this

Canonical Notch signaling plays an instructive role in auditory supporting cell development. / Campbell, Dean P.; Chrysostomou, Elena; Doetzlhofer, Angelika.

In: Scientific Reports, Vol. 6, 19484, 20.01.2016.

Research output: Contribution to journalArticle

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