Long-range migration of centrioles to the apical surface of the olfactory epithelium

Olfactory sensory neurons (OSNs) in vertebrates detect odorants using multiple cilia, which protrude from the end of the dendrite and require centrioles for their formation. In mouse olfactory epithelium, the centrioles originate in progenitor cells near the basal lamina, often 50 to 100 μm from the apical surface. It is unknown how centrioles traverse this distance or mature to form cilia. Using high-resolution expansion microscopy, we found that centrioles migrate together, with multiple centrioles per group and multiple groups per OSN, during dendrite outgrowth. Centrioles were found by live imaging to migrate slowly, with a maximum rate of 0.18 μm/min. Centrioles in migrating groups were associated with microtubule nucleation factors, but acquired rootletin and appendages only in mature OSNs. The parental centriole had preexisting appendages, formed a single cilium prior to other centrioles, and retained its unique appendage configuration in the mature OSN. We developed an air-liquid interface explant culture system for OSNs and used it to show that centriole migration can be perturbed ex vivo by stabilizing microtubules. We consider these results in the context of a comprehensive model for centriole formation, migration, and maturation in this important sensory cell type.

Oral Antioxidant Vitamins and Magnesium Limit Noise-Induced Hearing Loss by Promoting Sensory Hair Cell Survival: Role of Antioxidant Enzymes and Apoptosis Genes

Noise induces oxidative stress in the cochlea followed by sensory cell death and hearing loss. The proof of principle that injections of antioxidant vitamins and Mg2+ prevent noise-induced hearing loss (NIHL) has been established. However, effectiveness of oral administration remains controversial and otoprotection mechanisms are unclear. Using auditory evoked potentials, quantitative PCR, and immunocytochemistry, we explored effects of oral administration of vitamins A, C, E, and Mg2+ (ACEMg) on auditory function and sensory cell survival following NIHL in rats. Oral ACEMg reduced auditory thresholds shifts after NIHL. Improved auditory function correlated with increased survival of sensory outer hair cells. In parallel, oral ACEMg modulated the expression timeline of antioxidant enzymes in the cochlea after NIHL. There was increased expression of glutathione peroxidase-1 and catalase at 1 and 10 days, respectively. Also, pro-apoptotic caspase-3 and Bax levels were diminished in ACEMg-treated rats, at 10 and 30 days, respectively, following noise overstimulation, whereas, at day 10 after noise exposure, the levels of anti-apoptotic Bcl-2, were significantly increased. Therefore, oral ACEMg improves auditory function by limiting sensory hair cell death in the auditory receptor following NIHL. Regulation of the expression of antioxidant enzymes and apoptosis-related proteins in cochlear structures is involved in such an otoprotective mechanism.

Oral Antioxidant Vitamins and Magnesium Limit Noise-induced Hearing Loss by Promoting Sensory Hair Cell Survival: Role of Antioxidant Enzymes and Apoptosis Genes

Noise induces oxidative stress in the cochlea followed by sensory cell death and hearing loss. The proof of principle that injections of antioxidant vitamins and Mg2+ prevent noise-induced hearing loss (NIHL) has been established. However, effectiveness of oral administration remains controversial and otoprotection mechanisms unclear. Using auditory evoked potentials, quantitative PCR and immunocytochemistry, we explored effects of oral administration of vitamins A, C, E and Mg2+ (ACEMg) on auditory function and sensory cell survival following NIHL in rats. Oral ACEMg reduced auditory thresholds shifts after NIHL. Improved auditory function correlated with increased survival of sensory outer hair cells. In parallel, oral ACEMg modulated the expression timeline of antioxidant enzymes in the cochlea after NIHL. There was increased expression of Glutathione peroxidase-1 and Catalase at 1 and 10 days, respectively. Also, pro-apoptotic Caspase-3 and Bax levels were diminished in ACEMg-treated rats, at 10 and 30 days, respectively, following noise overstimulation, whereas, at day 10 after noise exposure, the levels of anti-apoptotic Bcl-2, were significantly increased. Therefore, oral ACEMg improves auditory function by limiting sensory hair cell death in the auditory receptor following NIHL. Regulation of the expression of antioxidant enzymes and apoptosis-related proteins in cochlear structures is involved in such otoprotective mechanism.

Dual regulation of planar polarization by secreted Wnts and Vangl2 in the developing mouse cochlea

ABSTRACTPlanar cell polarity (PCP) proteins localize asymmetrically to instruct cell polarity within the tissue plane, with defects leading to deformities of the limbs, neural tube and inner ear. Wnt proteins are evolutionarily conserved polarity cues, yet Wnt mutants display variable PCP defects; thus, how Wnts regulate PCP remains unresolved. Here, we have used the developing cochlea as a model system to show that secreted Wnts regulate PCP through polarizing a specific subset of PCP proteins. Conditional deletion of Wntless or porcupine, both of which are essential for secretion of Wnts, caused misrotated sensory cells and shortened cochlea – both hallmarks of PCP defects. Wntless-deficient cochleae lacked the polarized PCP components dishevelled 1/2 and frizzled 3/6, while other PCP proteins (Vangl1/2, Celsr1 and dishevelled 3) remained localized. We identified seven Wnt paralogues, including the major PCP regulator Wnt5a, which was, surprisingly, dispensable for planar polarization in the cochlea. Finally, Vangl2 haploinsufficiency markedly accentuated sensory cell polarization defects in Wntless-deficient cochlea. Together, our study indicates that secreted Wnts and Vangl2 coordinate to ensure proper tissue polarization during development.

Comparative micromechanics of bushcricket ears with and without a specialized auditory fovea region in the crista acustica

In some insects and vertebrate species, the specific enlargement of sensory cell epithelium facilitates the perception of particular behaviourally relevant signals. The insect auditory fovea in the ear of the bushcricket Ancylecha fenestrata (Tettigoniidae: Phaneropterinae) is an example of such an expansion of sensory epithelium. Bushcricket ears developed in convergent evolution anatomical and functional similarities to mammal ears, such as travelling waves and auditory foveae, to process information by sound. As in vertebrate ears, sound induces a motion of this insect hearing organ (crista acustica), which can be characterized by its amplitude and phase response. However, detailed micromechanics in this bushcricket ear with an auditory fovea are yet unknown. Here, we fill this gap in knowledge for bushcricket, by analysing and comparing the ear micromechanics in Ancylecha fenestrata and a bushcricket species without auditory fovea ( Mecopoda elongata , Tettigoniidae: Mecopodinae) using laser-Doppler vibrometry. We found that the increased size of the crista acustica, expanded by a foveal region in A. fenestrata , leads to higher mechanical amplitudes and longer phase delays in A. fenestrata male ears. Furthermore, area under curve analyses of the organ oscillations reveal that more sensory units are activated by the same stimuli in the males of the auditory fovea-possessing species A. fenestrata . The measured increase of phase delay in the region of the auditory fovea supports the conclusion that tilting of the transduction site is important for the effective opening of the involved transduction channels. Our detailed analysis of sound-induced micromechanics in this bushcricket ear demonstrates that an increase of sensory epithelium with foveal characteristics can enhance signal detection and may also improve the neuronal encoding.

LINKAGES OF Ca V1.2, GLUTAMATE, AND ODONTOBLAST IN THE MECHANISM OF TOOTH PAIN

Background: Odontoblast is often associated with its role as sensory cell in tooth pain. Odontoblasts have ion channels that contribute to the sensitivity and release of neurotransmitters in odontoblast stimuli that are activated in pulp sensory nerve fibers. Review: Ca V1.2 has unexpected plasticity. In dental injury, the appearance of Ca V1.2 canal in odontoblast is known to change, depend on the duration of injury. The dentinal pulp tissue has the ability to release glutamate, which acts as an intercellular mediator to create neuronal signaling communication between inter-odontoblast and odontoblast- trigeminal ganglion nerve (TG). Discussion: Odontoblasts as a mechanosensitive sensory cell are indicated by the role of the TRP transduction receptor and the release of ATP. Though other canals and active compounds in odontoblast are involved, an important role in delivering the sensation of pain also needs to be known. Odontoblast will communicate with paracrine pulp nerves using ATP and glutamate. Ca2+ enters the odontoblast through activated TRP channels and other ion channels, such as L-type VGCC channels (Ca V 1.2). Followed by the release of glutamate from odontoblast through the glutamate-permeable canal, it can trigger the pulp nerve via glutamate metabotropic receptors (mGluRs). Conclusion: There is involvement of Ca V1.2 and glutamate canals in odontoblast in the delivery mechanism of pain.

Comparing Sensory Organs to Define the Path for Hair Cell Regeneration

Deafness or hearing deficits are debilitating conditions. They are often caused by loss of sensory hair cells or defects in their function. In contrast to mammals, nonmammalian vertebrates robustly regenerate hair cells after injury. Studying the molecular and cellular basis of nonmammalian vertebrate hair cell regeneration provides valuable insights into developing cures for human deafness. In this review, we discuss the current literature on hair cell regeneration in the context of other models for sensory cell regeneration, such as the retina and the olfactory epithelium. This comparison reveals commonalities with, as well as differences between, the different regenerating systems, which begin to define a cellular and molecular blueprint of regeneration. In addition, we propose how new technical advances can address outstanding questions in the field.