Brandon Cox, PhD
Hearing loss is primarily caused by damage to specialized cells (called hair cells) that detect sound waves traveling through the cochlea of the inner ear. Non-mammalian vertebrates, such as birds, fish, and amphibians, can regenerate their hair cells after damage, while damage to auditory hair cells in mammals is currently thought to be permanent. We have recently developed a genetic method to damage hair cells in the neonatal mouse in vivo and discovered that, in contrast to common belief, the mouse cochlea does have the capacity to regenerate its hair cells
after damage. However, when hair cell death was induced at one week of age, no evidence of regeneration was detected.
The goals of my laboratory are to build upon these findings and investigate the cell source, mechanism, and genes involved in hair cell regeneration in the neonatal mouse cochlea. We are also interested the developmental changes that take place during the first postnatal weeks that prevent regeneration from occurring in juvenile and adult mice. We use mouse genetics (Cre/LoxP and tetracycline inducible systems) to manipulate gene expression in specific cell types at specific ages, as well as fate mapping to trace the origin of the regenerated hair cells.
|YFP (green) labeled hair cells in the apical turn of the cochlea in Atoh1-CreER; Rosa26-YFP mice given tamoxifen at birth.|
Newly regenerated hair cells in the neonatal mouse cochlea. Myosin VIIa (red) is a ubiquitous hair cell marker. Prestin (green) is specifically expressed in differentiated outer hair cells. EdU (white) labels cells that had previously divided.
Mellado Lagarde, MM, Cox BC, Fang J, Taylor R, Forge A and Zuo J. (2013) Selective ablation of pillar and Deiters’ cells severely affects cochlear postnatal development and hearing function in mice. J Neurosci 33:1564-1576.
Liu Z, Walters BJ, Owen T, Brimble MA, Steigelman KA, Zhang L, Mellado Lagarde MM, Valentine MB, Yu Y, Cox BC and Zuo J. (2012) Regulation of p27Kip1 by Sox2 maintains quiescence of inner pillar cells in the murine auditory sensory epithelium. J Neurosci 32:10530-10540.
Burns J*, Cox BC*, Thiede BR, Zuo J and Corwin JT. (2012) In vivo proliferative regeneration of balance hair cells in newborn mice. J Neurosci 32:6570-6577.
*authors contributed equally
-image chosen for journal cover
-selected by Faculty of 1000: Groves A: 2012. http://f1000.com/715348057#eval790903108
Cox BC, Liu Z, Mellado Lagarde MM and Zuo J. (2012) Conditional gene expression in the mouse inner ear using Cre-loxP. J Assoc Res Otolaryngol 13:295-322.
Liu Z, Dearman JA, Cox BC, Walters BJ, Zhang L, Ayrault O, Zindy F, Gan L, Roussel M, and Zuo J. (2012) Age-dependent in vivo conversion of mouse cochlear pillar and Dieters’ cells to immature hair cells by Atoh1 ectopic expression. J Neurosci 32: 6600-6610.
-selected by Faculty of 1000: Groves A: 2012. http://f1000.com/715348058#eval790903109
and Fekete D: 2012. http://f1000.com/715348058#eval791803011
Yu Y, Weber T, Yamashita Y, Liu Z, Valentine MB, Cox BC and Zuo J. (2010) In vivo proliferation of postmitotic cochlear supporting cells by acute ablation of the retinoblastoma protein in neonatal mice. J Neurosci 30: 5927-5936.
Cox BC, Marritt AM, Perry DC and Kellar KJ. (2008) Transport of multiple nicotinic acetylcholine receptors in the rat optic nerve: High densities of receptors containing α6 and β3 subunits. J Neurochem 105: 1924-1938.
Marritt AM, Cox BC, Yasuda RP, McIntosh JM, Xiao Y, Wolfe BB and Kellar KJ. (2005) Nicotinic cholinergic receptors in the rat retina: simple and mixed heteromeric subtypes. Mol Pharmacol 68: 1656-1668.
Kingsley RJ, Affif E, Cox BC, Kothari S, Kriechbaum K, Kuchinsky K, Neill AT, Puri AF and Kish VM. (2003) Expression of heat shock and cold shock proteins in the gorgonian Leptogorgia virgulata. J Exp Zoolog A Comp Exp Biol 296: 98-107.