Spontaneous hair cell regeneration in the neonatal mouse cochlea in vivo

Abstract

There was an error published in Development 141, 816-829.Edwin W. Rubel was omitted from the authorship of the paper. The correct author list and affiliations appears above.In addition the Acknowledgements and Author contributions sections should read as follows. AcknowledgementsWe thank L. Tong and R. Palmiter (University of Washington) for Pou4f3DTR/+ mice and discussion; S. Baker (St. Jude) for Atoh1-CreERTM mice and discussion; R. Kageyama (Kyoto University) for Hes5-nlsLacZ mice; P. Chambon (Institut Genetique Biologie Moleculaire Cellulaire) for the CreERT2 construct; S. Heller (Stanford University) for the anti-espin antibody and critical reading, J. Corwin, J. Burns and other members of the Corwin laboratory (University of Virginia) as well as members of our laboratories for discussion and critical comments; S. Connell, V. Frohlich, Y. Ouyang and J. Peters (St. Jude) for expertise in confocal imaging; A. Xue, V. Nookala, N.

Postnatal development, maturation and aging in the mouse cochlea and their effects on hair cell regeneration

“…However, an inability to recapitulate definitive HC regeneration in vivo (Lenoir et al, 1997; Parietti et al, 1998) cast doubt on the true regenerative potential of the neonatal rodent cochlea, and suggested that either culture conditions do not accurately recapitulate the native cochlear environment or that a method to damage HCs more acutely in vivo was required. Indeed, recent data from our lab and others suggest that, while constitutive proliferation of HCs and SCs has eluded detection beyond embryonic day (E)14.5 in the intact mouse cochlea, the expression of proliferating cell nuclear antigen (PCNA) persists postnatally (see Figure 1), new HCs continue to be added to the mouse cochlea when examined at postnatal day (P) 0 and P6 (Jan et al, Unpublished), and rapidly acute HC loss during the first postnatal week, in vivo , results in proliferation, differentiation, and a robust, if transient, regeneration of lost HCs (Cox et al, 2012a). Despite such promising findings, this first postnatal week appears to represent a critical window during which such endogenous regeneration and proliferation can occur (Cox et al, 2012a).…”

Mammalian Cochlear Hair Cell Regeneration and Ribbon Synapse Reformation

“…In the recent years, there is growing concern about the HC regeneration and synaptic plasticity around the globe and the great achievements have been made in revealing the mechanism and strategies to recover hearing function in mammals [10, 13, 59, 101]. Different levels of HC regeneration could be achieved through the regulation of factors and signaling pathways, which play important roles during the development of mammalian inner ear [23, 34, 48, 59].…”

“…Different levels of HC regeneration could be achieved through the regulation of factors and signaling pathways, which play important roles during the development of mammalian inner ear [23, 34, 48, 59]. Synapse and nerve fiber related markers are detected around the newly regenerated HCs [10, 34, 89]. However, we are still quite far from restoring the hearing function in the damaged inner ear.…”

“…In nonmammalian vertebrates such as birds, after ototoxic drugs or damaged by noise, the inner ear sensory HCs can regenerate spontaneously and eventually replace the damaged HCs, thus maintaining and restoring the function of sensory epithelium [5, 9]. However, in mammals, spontaneous HC regeneration in vivo has only been identified in neonatal cochleae and also the number of regenerated HCs is quite low; as a result the hearing loss is permanent in mammals [10, 11]. It is thought that the mammalian inner ear HCs and SCs originate from the common precursor cells and some of the reported studies suggested that some SCs become HCs when the microenvironment changes, such as damage to HCs and activation of particular genes; SCs can continue to differentiate to form HCs [12, 13].…”

“…Cochlear ribbon synapses have limited intrinsic capacity to spontaneously regenerate [86–88]. Prior study reported that when cochleae is damaged in neonatal mice, the HCs spontaneously regenerate from the SCs, but the inner cell marker vesicular glutamate transporter VGlut3 was not detected in these newly regenerated HCs [10]. When the Notch1 signaling pathway overactivated to induce the ectopic HCs, the neural fiber marker Tuj1 was detected in the lateral edge of spiral ganglion neuron, while the synaptic marker synaptophysin was detected between the new HCs and neuronal cells in the spiral ganglion regions, but the synaptophysin signals adjacent to new HCs were weaker indicating that the synaptic structures among new HCs and neuronal cells were not fully mature [89].…”