NDLI: In vivo proliferation of postmitotic cochlear supporting cells by acute ablation of the retinoblastoma protein in neonatal mice

Content Provider	PubMed Central
Author	Yu, Yiling Weber, Thomas Yamashita, Tetsuji Liu, Zhiyong Valentine, Marcus B. Cox, Brandon C. Zuo, Jian
Abstract	Cochlear hair cells (HCs) are mechanosensory receptors that transduce sound into electrical signals. HC damage in non-mammalian vertebrates induces surrounding supporting cells (SCs) to divide, transdifferentiate and replace lost HCs; however, such spontaneous HC regeneration does not occur in the mammalian cochlea. Here, we acutely ablate the retinoblastoma protein (Rb), a crucial cell cycle regulator, in two subtypes of postmitotic SCs (pillar and Deiters’ cells) using an inducible Cre line, Prox1-CreERT2 . Inactivation of Rb in these SCs results in cell cycle reentry of both pillar and Deiters’ cells, and completion of cell division with an increase in cell number of pillar cells. Interestingly, nuclei of Rb −/− mitotic pillar and Deiters’ cells migrate toward the HC layer and divide near the epithelial surface in a manner similar to the SCs in the regenerating avian auditory epithelium. In contrast to postmitotic Rb −/− HCs which abort cell division, postmitotic Rb −/− pillar cells can proliferate, maintain their SC fate and survive for more than a week. However, no newly formed HCs are detected and SC death followed by HC loss occurs. Our studies accomplish a crucial step toward functional HC regeneration in the mammalian cochlea in vivo, demonstrating the critical role of Rb in maintaining quiescence of postmitotic pillar and Deiters’ cells and highlighting the heterogeneity between these two cell types. Therefore, the combination of transient Rb inactivation and further manipulation of transcription factors (i.e., Atoh1 activation) in SCs may represent an effective therapeutic avenue for HC regeneration in the mammalian cochlea.
Related Links	http://dx.doi.org/10.1523/jneurosci.5989-09.2010
Ending Page	5936
Page Count	10
Starting Page	5927
File Format	PDF
ISSN	02706474
e-ISSN	15292401
Journal	The Journal of neuroscience : the official journal of the Society for Neuroscience
Issue Number	17
Volume Number	30
Language	English
Publisher Date	2010-04-28
Access Restriction	Open
Subject Keyword	Neuroscience(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Neuroscience

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Spontaneous regeneration of cochlear supporting cells after neonatal ablation ensures hearing in the adult mouse

Selective ablation of pillar and Deiters’ cells severely affects cochlear postnatal development and hearing in mice

MYC Gene Delivery to Adult Mouse Utricles Stimulates Proliferation of Postmitotic Supporting Cells In Vitro

Spontaneous regeneration of cochlear supporting cells after neonatal ablation ensures hearing in the adult mouse.

Age-dependent in vivo conversion of mouse cochlear pillar and Deiters’ cells to immature hair cells by Atoh1 ectopic expression

Sox2-CreER mice are useful for fate mapping of mature, but not neonatal, cochlear supporting cells in hair cell regeneration studies

Connexin26 expression in brain parenchymal cells demonstrated by targeted connexin ablation in transgenic mice

Bmi1 Regulates the Proliferation of Cochlear Supporting Cells Via the Canonical Wnt Signaling Pathway

Sox2-CreER mice are useful for fate mapping of mature, but not neonatal, cochlear supporting cells in hair cell regeneration studies

In vivo proliferation of postmitotic cochlear supporting cells by acute ablation of the retinoblastoma protein in neonatal mice

Similar Documents

Spontaneous regeneration of cochlear supporting cells after neonatal ablation ensures hearing in the adult mouse

Selective ablation of pillar and Deiters’ cells severely affects cochlear postnatal development and hearing in mice

MYC Gene Delivery to Adult Mouse Utricles Stimulates Proliferation of Postmitotic Supporting Cells In Vitro

Spontaneous regeneration of cochlear supporting cells after neonatal ablation ensures hearing in the adult mouse.

Age-dependent in vivo conversion of mouse cochlear pillar and Deiters’ cells to immature hair cells by Atoh1 ectopic expression

Sox2-CreER mice are useful for fate mapping of mature, but not neonatal, cochlear supporting cells in hair cell regeneration studies

Connexin26 expression in brain parenchymal cells demonstrated by targeted connexin ablation in transgenic mice

Bmi1 Regulates the Proliferation of Cochlear Supporting Cells Via the Canonical Wnt Signaling Pathway

Sox2-CreER mice are useful for fate mapping of mature, but not neonatal, cochlear supporting cells in hair cell regeneration studies

In vivo proliferation of postmitotic cochlear supporting cells by acute ablation of the retinoblastoma protein in neonatal mice