Defining the Cellular Environment in the Organ of Corti following Extensive Hair Cell Loss: A Basis for Future Sensory Cell Replacement in the Cochlea

Background: Following the loss of hair cells from the mammalian cochlea, the sensory epithelium repairs to close the lesions but no new hair cells arise and hearing impairment ensues. For any cell replacement strategy to be successful, the cellular environment of the injured tissue has to be able to nurture new hair cells. This study defines characteristics of the auditory sensory epithelium after hair cell loss. Methodology/Principal Findings: Studies were conducted in C57BL/6 and CBA/Ca mice. Treatment with an aminoglycoside-diuretic combination produced loss of all outer hair cells within 48 hours in both strains. The subsequent progressive tissue re-organisation was examined using immunohistochemistry and electron microscopy. There was no evidence of significant de-differentiation of the specialised columnar supporting cells. Kir4.1 was down regulated but KCC4, GLAST, microtubule bundles, connexin expression patterns and pathways of intercellular communication were retained. The columnar supporting cells became covered with non-specialised cells migrating from the outermost region of the organ of Corti. Eventually non-specialised, flat cells replaced the columnar epithelium. Flat epithelium developed in distributed patches interrupting regions of columnar epithelium formed of differentiated supporting cells. Formation of the flat epithelium was initiated within a few weeks post-treatment in C57BL/6 mice but not for several months in CBA/Ca’s, suggesting genetic background influences the rate of re-organisation

Structure and Function of the Hair Cell Ribbon Synapse

Faithful information transfer at the hair cell afferent synapse requires synaptic transmission to be both reliable and temporally precise. The release of neurotransmitter must exhibit both rapid on and off kinetics to accurately follow acoustic stimuli with a periodicity of 1 ms or less. To ensure such remarkable temporal fidelity, the cochlear hair cell afferent synapse undoubtedly relies on unique cellular and molecular specializations. While the electron microscopy hallmark of the hair cell afferent synapse — the electron-dense synaptic ribbon or synaptic body — has been recognized for decades, dissection of the synapse’s molecular make-up has only just begun. Recent cell physiology studies have added important insights into the synaptic mechanisms underlying fidelity and reliability of sound coding. The presence of the synaptic ribbon links afferent synapses of cochlear and vestibular hair cells to photoreceptors and bipolar neurons of the retina. This review focuses on major advances in understanding the hair cell afferent synapse molecular anatomy and function that have been achieved during the past years

Prominent Actin Fiber Arrays in Drosophila Tendon Cells Represent Architectural Elements Different from Stress Fibers

Tendon cells are specialized cells of the insect epidermis that connect basally attached muscle tips to the cuticle on their apical surface via prominent arrays of microtubules. Tendon cells of Drosophila have become a useful genetic model system to address questions with relevance to cell and developmental biology. Here, we use light, confocal, and electron microscopy to present a refined model of the subcellular organization of tendon cells. We show that prominent arrays of F-actin exist in tendon cells that fully overlap with the microtubule arrays, and that type II myosin accumulates in the same area. The F-actin arrays in tendon cells seem to represent a new kind of actin structure, clearly distinct from stress fibers. They are highly resistant to F-actin–destabilizing drugs, to the application of myosin blockers, and to loss of integrin, Rho1, or mechanical force. They seem to represent an important architectural element of tendon cells, because they maintain a connection between apical and basal surfaces even when microtubule arrays of tendon cells are dysfunctional. Features reported here and elsewhere for tendon cells are reminiscent of the structural and molecular features of support cells in the inner ear of vertebrates, and they might have potential translational value