Spontaneous Hair Cell Regeneration Is Prevented by Increased Notch Signaling in Supporting Cells

Frontiers in Cellular Neuroscience
Melissa M McGovernBrandon C Cox

Abstract

During embryonic development, differentiation of cochlear progenitor cells into hair cells (HCs) or supporting cells (SCs) is partially controlled through Notch signaling. Many studies have shown that inhibition of Notch signaling allows SCs to convert into HCs in both normal and drug damaged neonatal mouse cochleae. This mechanism is also implicated during HC regeneration in non-mammalian vertebrates; however, the mechanism of spontaneous HC regeneration in the neonatal mouse cochlea is less understood. While inhibition of Notch signaling can force SCs to convert into HCs and increase the number of regenerated HCs, it is currently unknown whether this pathway is involved in spontaneous HC regeneration observed in vivo. Therefore, we investigated the role of Notch signaling during the spontaneous HC regeneration process using Atoh1-CreERTM::Rosa26loxP-stop-loxP-DTA/+ mice injected with tamoxifen at postnatal day (P) 0 and P1 to ablate HCs and stimulate spontaneous HC regeneration. Expression changes of genes in the Notch pathway were measured using immunostaining and in situ hybridization, with most changes observed in the apical one-third of the cochlea where the majority of HC regeneration occurs. Expression of the Notch targ...Continue Reading

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Citations

Mar 4, 2020·Biomolecules·Rogers Brown, Andrew K Groves
Dec 5, 2019·The Journal of the Acoustical Society of America·Rick P C Cousins
Jan 27, 2019·Hearing Research·Bradley J Walters, Brandon C Cox
Aug 11, 2021·Current Opinion in Otolaryngology & Head and Neck Surgery·Zhengqing HuNathan Sim
Sep 23, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Ali Akbar SamadaniMagtouf Gatei

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Methods Mentioned

BETA
in vitro transcription
transgenic

Software Mentioned

Graphpad
Graphpad Prism
BLAST

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