The stat3/socs3a Pathway Is a Key Regulator of Hair Cell Regeneration in Zebrafish stat3/socs3a Pathway: Regulator of Hair Cell Regeneration
- Authors
- Liang, J., Wang, D., Renaud, G., Wolfsberg, T.G., Wilson, A.F., and Burgess, S.M.
- ID
- ZDB-PUB-120807-33
- Date
- 2012
- Source
- The Journal of neuroscience : the official journal of the Society for Neuroscience 32(31): 10662-10673 (Journal)
- Registered Authors
- Burgess, Shawn
- Keywords
- none
- MeSH Terms
-
- Signal Transduction/drug effects
- Signal Transduction/physiology*
- Noise/adverse effects
- Chi-Square Distribution
- STAT3 Transcription Factor/genetics
- STAT3 Transcription Factor/metabolism*
- Analysis of Variance
- Regeneration/drug effects
- Regeneration/physiology*
- Gene Expression Regulation, Developmental/drug effects
- Gene Expression Regulation, Developmental/physiology*
- RNA, Messenger/administration & dosage
- Bromodeoxyuridine/metabolism
- Cell Proliferation
- Lateral Line System/cytology
- Lateral Line System/drug effects
- Lateral Line System/growth & development
- Male
- Cell Death/drug effects
- Copper Sulfate/pharmacology
- Hair Cells, Auditory/drug effects
- Hair Cells, Auditory/physiology*
- Green Fluorescent Proteins/genetics
- Green Fluorescent Proteins/metabolism
- Cell Count
- Larva
- Neural Inhibition/drug effects
- Neural Inhibition/genetics
- Morpholinos/pharmacology
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- Animals
- Cell Differentiation/physiology
- Suppressor of Cytokine Signaling Proteins/genetics
- Suppressor of Cytokine Signaling Proteins/metabolism*
- Female
- PubMed
- 22855815 Full text @ J. Neurosci.
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.