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Inhibition of Notch/RBP-J signaling induces hair cell formation in neonate mouse cochleas.
- Source :
-
Journal of molecular medicine (Berlin, Germany) [J Mol Med (Berl)] 2006 Jan; Vol. 84 (1), pp. 37-45. Date of Electronic Publication: 2005 Nov 08. - Publication Year :
- 2006
-
Abstract
- Mammalian inner ear hair cells in cochleas are believed to be incapable of regeneration after birth, which hampers treatment of sensorineural hearing impairment mainly caused by hair cell loss. Sensory epithelia of cochleas are composed of hair cells and supporting cells, both of which originate from common progenitors. Notch/RBP-J signaling is an evolutionally conserved pathway involved in specification of various cell types in developmental stage and even in some of postnatal mammalian organs. The specification of hair cell fate from the progenitors is inhibited by Notch/RBP-J signaling in embryonic inner ears. However, its function in postnatal inner ears is unknown. We showed that inhibition of Notch/RBP-J signaling, by either conditional disruption of the Rbpsuh gene or treatment with a gamma-secretase inhibitor, could give rise to ectopic hair cells in the supporting cell region in organs of Corti from neonatal mouse cochleas where hair cells have not been considered to regenerate after birth. We also showed that down-regulation of Hes5 and up-regulation of Math1 were associated with ectopic hair cell induction. These results suggest that Notch/RBP-J signaling inhibits supporting cells from differentiation into hair cells even in postnatal days, implying that inhibitors of Notch/RBP-J signaling can be used to help regenerating hair cells after birth and thus serve for potential treatment of intractable sensorineural hearing impairment caused by hair cell loss without genetical manipulation.
- Subjects :
- Animals
Animals, Newborn
Basic Helix-Loop-Helix Transcription Factors genetics
Basic Helix-Loop-Helix Transcription Factors metabolism
Cochlea embryology
Cochlea growth & development
Dyneins metabolism
Embryonic Induction
Hair Cells, Auditory embryology
Hair Cells, Auditory metabolism
Immunoglobulin J Recombination Signal Sequence-Binding Protein genetics
Mice
Mice, Knockout
Morphogenesis
Myosin VIIa
Myosins metabolism
Receptors, Notch genetics
Repressor Proteins genetics
Repressor Proteins metabolism
Tissue Culture Techniques
Cochlea cytology
Hair Cells, Auditory growth & development
Immunoglobulin J Recombination Signal Sequence-Binding Protein metabolism
Receptors, Notch metabolism
Signal Transduction physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0946-2716
- Volume :
- 84
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of molecular medicine (Berlin, Germany)
- Publication Type :
- Academic Journal
- Accession number :
- 16283144
- Full Text :
- https://doi.org/10.1007/s00109-005-0706-9