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Responses to cell loss become restricted as the supporting cells in mammalian vestibular organs grow thick junctional actin bands that develop high stability.
- Source :
-
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2014 Jan 29; Vol. 34 (5), pp. 1998-2011. - Publication Year :
- 2014
-
Abstract
- Sensory hair cell (HC) loss is a major cause of permanent hearing and balance impairments for humans and other mammals. Yet, fish, amphibians, reptiles, and birds readily replace HCs and recover from such sensory deficits. It is unknown what prevents replacement in mammals, but cell replacement capacity declines contemporaneously with massive postnatal thickening of F-actin bands at the junctions between vestibular supporting cells (SCs). In non-mammals, SCs can give rise to regenerated HCs, and the bands remain thin even in adults. Here we investigated the stability of the F-actin bands between SCs in ears from chickens and mice and Madin-Darby canine kidney cells. Pharmacological experiments and fluorescence recovery after photobleaching (FRAP) of SC junctions in utricles from mice that express a γ-actin-GFP fusion protein showed that the thickening F-actin bands develop increased resistance to depolymerization and exceptional stability that parallels a sharp decline in the cell replacement capacity of the maturing mammalian ear. The FRAP recovery rate and the mobile fraction of γ-actin-GFP both decreased as the bands thickened with age and became highly stabilized. In utricles from neonatal mice, time-lapse recordings in the vicinity of dying HCs showed that numerous SCs change shape and organize multicellular actin purse strings that reseal the epithelium. In contrast, adult SCs appeared resistant to deformation, with resealing responses limited to just a few neighboring SCs that did not form purse strings. The exceptional stability of the uniquely thick F-actin bands at the junctions of mature SCs may play an important role in restricting dynamic repair responses in mammalian vestibular epithelia.
- Subjects :
- Actins genetics
Age Factors
Animals
Animals, Newborn
Bridged Bicyclo Compounds, Heterocyclic pharmacology
Cell Death drug effects
Cell Death genetics
Cells, Cultured
Chick Embryo
Cytochalasin D pharmacology
Dose-Response Relationship, Drug
Embryo, Mammalian
Epithelial Cells drug effects
Female
Gene Expression Regulation, Developmental drug effects
Intercellular Junctions drug effects
Intercellular Junctions genetics
Kidney cytology
Luminescent Proteins genetics
Luminescent Proteins metabolism
Male
Mice
Mice, Transgenic
Nucleic Acid Synthesis Inhibitors pharmacology
Occludin metabolism
Organ Culture Techniques
Thiazolidines pharmacology
Actins metabolism
Gene Expression Regulation, Developmental physiology
Intercellular Junctions metabolism
Labyrinth Supporting Cells physiology
Vestibule, Labyrinth cytology
Vestibule, Labyrinth embryology
Vestibule, Labyrinth growth & development
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2401
- Volume :
- 34
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 24478379
- Full Text :
- https://doi.org/10.1523/JNEUROSCI.4355-13.2014