ERBB is a Novel Candidate for Driving Mammalian Cochlear Regeneration
Başlık:
ERBB is a Novel Candidate for Driving Mammalian Cochlear Regeneration
Yazar:
Zhang, Jingyuan, author.
ISBN:
9780355974980
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (119 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-10(E), Section: B.
Advisors: Patricia M. White Committee members: Sina Ghaemmaghami; David S. Goldfarb; Catherine E. Ovitt; Christoph Proschel; Andrei Seluanov.
Özet:
Hearing is the ability to detect and perceive sound, an important quality in human activities. Hearing loss may happen when cochlear hair cells (HCs) are damaged or lost due to various factors, such as ototoxic insults and exposure to noise. In mammals, HCs are not regenerated once they die, resulting in permanent hearing impairment. However, in other vertebrates, the adjacent supporting cells (SCs) spontaneously proliferate and differentiate into new HCs, leading to functional re-establishment. Here we report on the effects of expressing constitutively activated ERBB2 receptors (CA-ERBB2) in mouse cochlear SCs. We used a variety of methods, including viruses, transgenic expression, and small molecules interventions, to achieve ERBB2 gain-of-function activity at early stage. In vitro, lineage-labeled SCs that harbored CA-ERBB2 appeared to signal to their neighboring SCs, inducing them to down-regulate SC marker SOX2 expression and to proliferate. In vivo, we found supernumerary HC-like cells near lineage-labeled SCs. Both of these findings were largely reproduced using small molecules that activate ERBB signaling. We then tested CA-ERBB2 in adult cochlear SCs under normal and noise damage conditions. We found that CA-ERBB2 signaling up-regulated the HC specification gene Atoh1. CA-ERBB2 stimulated the formation of unique sphere-like cell clusters in adult mouse cochlea. More strikingly, we observed some improvement of hearing in one animal at three months after noise. Our data support a model wherein manipulation of ERBB expression may drive the activation of secondary signaling pathways that initiate HC regeneration, or promote functional recovery through some other mechanisms. Thus, this work may be of benefit towards the discovery of therapeutic targets to treat hearing loss.
Notlar:
School code: 0188
Tüzel Kişi Ek Girişi:
Mevcut:*
Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(680133.1) | 680133-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
On Order
Liste seç
Bunu varsayılan liste yap.
Öğeler başarıyla eklendi
Öğeler eklenirken hata oldu. Lütfen tekrar deneyiniz.
:
Select An Item
Data usage warning: You will receive one text message for each title you selected.
Standard text messaging rates apply.