[Top] [All Lists]

Bioacoustic paper in Nature‏‏‏‏

To: <>
Subject: Bioacoustic paper in Nature‏‏‏‏
From: Jianqiang XIAO <>
Date: Mon, 29 Sep 2008 03:11:49 +0800
Nature 455

Editor's Summary
Hair-cell triggers
Cochlear hair cells form the sound-sensing apparatus of vertebrates and their 
loss or damage results in hearing impairment. Mammals cannot regenerate these 
cells, but previous work has shown that ectopic expression of the transcription 
factor Atonal homologue 1 (Atoh1) can induce cells that would not normally 
differentiate as cochlear hair cells to become hair cell-like. Now Gubbels et 
al. show that in utero gene transfer of Atoh1 into mouse cochleas generates 
ectopic hair cells in the cochlea. Importantly, these supernumerary hair cells 
are functionally competent and display neuronal connectivity. This is a major 
step towards experiments to test for the ability of gene therapies to 
ameliorate hearing loss in mouse models of human deafness.

Authors: Making the paper: John Brigande
Tuning in to how genes control hearing development.

News and Views: Hearing: Route to authentic hair cells
Mats Ulfendahl
Existing therapies for hearing defects are generally ineffective in severe 
forms of deafness. A technical feat that generates sound-sensing hair cells in 
the inner ear of mice might have long-term potential.

Nature 455, 537-541 (25 September 2008) | doi:10.1038/nature07265
Functional auditory hair cells produced in the mammalian cochlea by in utero 
gene transfer
Samuel P. Gubbels1,4,5, David W. Woessner1,4,5, John C. Mitchell2, Anthony J. 
Ricci3 & John V. Brigande1
   1. Department of Otolaryngology, Oregon Hearing Research Center, and,
   2. Department of Restorative Dentistry, Division of Biomaterials and 
Biomechanics, School of Dentistry, Oregon Health & Science University, 3181 SW 
Sam Jackson Park Road, Portland, Oregon 97239, USA
   3. Department of Otolaryngology-Head and Neck Surgery, Stanford University 
School of Medicine, 801 Welch Road, Stanford, California 94305, USA
   4. These authors contributed equally to this work.
   5. Present addresses: Department of Surgery, Division of Otolaryngology, 
University of Wisconsin – Madison, K4/719 CSC, 600 Highland Avenue, Madison, 
Wisconsin 53792, USA (S.P.G.); Department of Pharmacology and Toxicology, 
University of Utah, College of Pharmacy, 30 South 2000 East, Room 201, Salt 
Lake City, Utah 84112, USA (D.W.W.).
Correspondence to: John V. Brigande1 Correspondence and requests for materials 
should be addressed to J.V.B. (Email: 
Sensory hair cells in the mammalian cochlea convert mechanical stimuli into 
electrical impulses that subserve audition1, 2. Loss of hair cells and their 
innervating neurons is the most frequent cause of hearing impairment3. Atonal 
homologue 1 (encoded by Atoh1, also known as Math1) is a basic helix–loop–helix 
transcription factor required for hair-cell development4, 5, 6, and its 
misexpression in vitro 7, 8 and in vivo 9, 10 generates hair-cell-like cells. 
Atoh1-based gene therapy to ameliorate auditory10 and vestibular11 dysfunction 
has been proposed. However, the biophysical properties of putative hair cells 
induced by Atoh1 misexpression have not been characterized. Here we show that 
in utero gene transfer of Atoh1 produces functional supernumerary hair cells in 
the mouse cochlea. The induced hair cells display stereociliary bundles, 
attract neuronal processes and express the ribbon synapse marker 
carboxy-terminal binding protein 2 (refs 12,13). Moreover, the hair cells a!

 re capable of mechanoelectrical transduction1, 2 and show basolateral 
conductances with age-appropriate specializations. Our results demonstrate that 
manipulation of cell fate by transcription factor misexpression produces 
functional sensory cells in the postnatal mammalian cochlea. We expect that our 
in utero gene transfer paradigm will enable the design and validation of gene 
therapies to ameliorate hearing loss in mouse models of human deafness14, 15.



XIAO, Jianqiang, Ph.D.
Research Associate
Psychology Department
Rutgers University
152 Frelinghuysen Road
Piscataway, NJ 08854

News, entertainment and everything you care about at Get it now!

<Prev in Thread] Current Thread [Next in Thread>
  • Bioacoustic paper in Nature‏‏‏‏, Jianqiang XIAO <=

The University of NSW School of Computer and Engineering takes no responsibility for the contents of this archive. It is purely a compilation of material sent by many people to the Bioacoustics-L mailing list. It has not been checked for accuracy nor its content verified in any way. If you wish to get material removed from the archive or have other queries about the archive e-mail Andrew Taylor at this address: andrewt@cse.unsw.EDU.AU