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The stat3/socs3a pathway is a key regulator of hair cell regeneration in zebrafish. [corrected].
- Source :
-
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2012 Aug 01; Vol. 32 (31), pp. 10662-73. - Publication Year :
- 2012
-
Abstract
- All nonmammalian vertebrates studied can regenerate inner ear mechanosensory receptors (i.e., hair cells) (Corwin and Cotanche, 1988; Lombarte et al., 1993; Baird et al., 1996), but mammals possess only a very limited capacity for regeneration after birth (Roberson and Rubel, 1994). As a result, mammals experience permanent deficiencies in hearing and balance once their inner ear hair cells are lost. The mechanisms of hair cell regeneration are poorly understood. Because the inner ear sensory epithelium is highly conserved in all vertebrates (Fritzsch et al., 2007), we chose to study hair cell regeneration mechanism in adult zebrafish, hoping the results would be transferrable to inducing hair cell regeneration in mammals. We defined the comprehensive network of genes involved in hair cell regeneration in the inner ear of adult zebrafish with the powerful transcriptional profiling technique digital gene expression, which leverages the power of next-generation sequencing ('t Hoen et al., 2008). We also identified a key pathway, stat3/socs3, and demonstrated its role in promoting hair cell regeneration through stem cell activation, cell division, and differentiation. In addition, transient pharmacological inhibition of stat3 signaling accelerated hair cell regeneration without overproducing cells. Taking other published datasets into account (Sano et al., 1999; Schebesta et al., 2006; Dierssen et al., 2008; Riehle et al., 2008; Zhu et al., 2008; Qin et al., 2009), we propose that the stat3/socs3 pathway is a key response in all tissue regeneration and thus an important therapeutic target for a broad application in tissue repair and injury healing.
- Subjects :
- Analysis of Variance
Animals
Bromodeoxyuridine metabolism
Cell Count
Cell Death drug effects
Cell Differentiation physiology
Cell Proliferation
Chi-Square Distribution
Copper Sulfate pharmacology
Female
Gene Expression Regulation, Developmental drug effects
Green Fluorescent Proteins genetics
Green Fluorescent Proteins metabolism
Hair Cells, Auditory drug effects
Larva
Lateral Line System cytology
Lateral Line System drug effects
Lateral Line System growth & development
Male
Morpholinos pharmacology
Neural Inhibition drug effects
Neural Inhibition genetics
Noise adverse effects
RNA, Messenger administration & dosage
Regeneration drug effects
STAT3 Transcription Factor genetics
Signal Transduction drug effects
Suppressor of Cytokine Signaling 3 Protein
Suppressor of Cytokine Signaling Proteins genetics
Zebrafish
Zebrafish Proteins genetics
Gene Expression Regulation, Developmental physiology
Hair Cells, Auditory physiology
Regeneration physiology
STAT3 Transcription Factor metabolism
Signal Transduction physiology
Suppressor of Cytokine Signaling Proteins metabolism
Zebrafish Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2401
- Volume :
- 32
- Issue :
- 31
- Database :
- MEDLINE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 22855815
- Full Text :
- https://doi.org/10.1523/JNEUROSCI.5785-10.2012