RESUMO
The inner ear contains six distinct sensory organs that each maintains some ability to regenerate hair cells into adulthood. In the postnatal cochlea, there appears to be a relationship between the developmental maturity of a region and its ability to regenerate as postnatal regeneration largely occurs in the apical turn, which is the last region to differentiate and mature during development. In the mature cristae there are also regional differences in regenerative ability, which led us to hypothesize that there may be a general relationship between the relative maturity of a region and the regenerative competence of that region in all of the inner ear sensory organs. By analyzing adult mouse cristae labeled embryonically with BrdU, we found that hair cell birth starts in the central region and progresses to the periphery with age. Since the peripheral region of the adult cristae also maintains active Notch signaling and some regenerative competence, these results are consistent with the hypothesis that the last regions to develop retain some of their regenerative ability into adulthood. Further, by analyzing embryonic day 14.5 inner ears we provide evidence for a wave of hair cell birth along the longitudinal axis of the cristae from the central regions to the outer edges. Together with the data from the adult inner ears labeled with BrdU as embryos, these results suggest that hair cell differentiation closely follows cell cycle exit in the cristae, unlike in the cochlea where they are uncoupled.
Assuntos
Ciclo Celular/fisiologia , Cóclea/embriologia , Células Ciliadas da Ampola/citologia , Células Ciliadas Auditivas/citologia , Organogênese/fisiologia , Animais , Bromodesoxiuridina/metabolismo , Diferenciação Celular , Feminino , Audição/fisiologia , Camundongos , Receptores Notch/metabolismo , Regeneração/fisiologia , Transdução de Sinais , Análise EspacialRESUMO
Sensory hair cells are mechanoreceptors of the auditory and vestibular systems and are crucial for hearing and balance. In adult mammals, auditory hair cells are unable to regenerate, and damage to these cells results in permanent hearing loss. By contrast, hair cells in the chick cochlea and the zebrafish lateral line are able to regenerate, prompting studies into the signaling pathways, morphogen gradients and transcription factors that regulate hair cell development and regeneration in various species. Here, we review these findings and discuss how various signaling pathways and factors function to modulate sensory hair cell development and regeneration. By comparing and contrasting development and regeneration, we also highlight the utility and limitations of using defined developmental cues to drive mammalian hair cell regeneration.
Assuntos
Orelha Interna/embriologia , Células Ciliadas da Ampola/citologia , Sistema da Linha Lateral/embriologia , Mecanorreceptores/citologia , Modelos Biológicos , Morfogênese/fisiologia , Regeneração/fisiologia , Fatores Etários , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/fisiologia , Ciclo Celular/fisiologia , Diferenciação Celular/fisiologia , Linhagem da Célula/fisiologia , Embrião de Galinha , Orelha Interna/citologia , Células Ciliadas da Ampola/fisiologia , Sistema da Linha Lateral/citologia , Mecanorreceptores/fisiologia , Camundongos , Especificidade da Espécie , Peixe-Zebra/embriologiaAssuntos
Técnicas de Cultura de Células , Orelha Interna/citologia , Células-Tronco Neurais/citologia , Células Neuroepiteliais/citologia , Neurogênese , Células-Tronco Pluripotentes/citologia , Estereocílios/ultraestrutura , Engenharia Tecidual/métodos , Animais , Polaridade Celular , Células Cultivadas , Ectoderma/citologia , Células Ciliadas da Ampola/citologia , Células Ciliadas da Ampola/ultraestrutura , Células Ciliadas Auditivas/citologia , Células Ciliadas Auditivas/ultraestrutura , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Filamentos Intermediários/ultraestrutura , Células Labirínticas de Suporte/citologia , Células Labirínticas de Suporte/ultraestrutura , Camundongos , Placa Neural/citologia , Células-Tronco Neurais/efeitos dos fármacos , Células Neuroepiteliais/ultraestrutura , Neurogênese/efeitos dos fármacos , Células-Tronco Pluripotentes/efeitos dos fármacos , Vestíbulo do Labirinto/citologiaRESUMO
In mammals, hair cells may be damaged or lost due to genetic mutation, infectious disease, chemical ototoxicity, noise and other factors, causing permanent sensorineural deafness. Regeneration of hair cells is a basic pre-requisite for recovery of hearing in deaf animals. The inner ear stem cells in the organ of Corti and vestibular utricle are the most ideal precursors for regeneration of inner ear hair cells. This review highlights some recent findings concerning the proliferation and differentiation of inner ear stem cells. The differentiation of inner ear stem cells into hair cells involves a series of signaling pathways and regulatory factors. This paper offers a comprehensive analysis of the related studies.
Assuntos
Diferenciação Celular/fisiologia , Orelha Interna/embriologia , Células Ciliadas da Ampola/fisiologia , Regeneração/fisiologia , Transdução de Sinais/fisiologia , Células-Tronco/fisiologia , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Orelha Interna/citologia , Células Ciliadas da Ampola/citologia , Camundongos , Receptores Notch/metabolismo , Células-Tronco/citologiaRESUMO
Weakly electric fish use electroreception for both active and passive electrolocation and for electrocommunication. While both active and passive electrolocation systems are prominent in weakly electric Mormyriform fishes, knowledge of their passive electrolocation ability is still scarce. To better estimate the contribution of passive electric sensing to the orientation toward electric stimuli in weakly electric fishes, we investigated frequency tuning applying classical input-output characterization and stimulus reconstruction methods to reveal the encoding capabilities of ampullary receptor afferents. Ampullary receptor afferents were most sensitive (threshold: 40 µV/cm) at low frequencies (<10 Hz) and appear to be tuned to a mix of amplitude and slope of the input signals. The low-frequency tuning was corroborated by behavioral experiments, but behavioral thresholds were one order of magnitude higher. The integration of simultaneously recorded afferents of similar frequency-tuning resulted in strongly enhanced signal-to-noise ratios and increased mutual information rates but did not increase the range of frequencies detectable by the system. Theoretically the neuronal integration of input from receptors experiencing opposite polarities of a stimulus (left and right side of the fish) was shown to enhance encoding of such stimuli, including an increase of bandwidth. Covariance and coherence analysis showed that spiking of ampullary afferents is sufficiently explained by the spike-triggered average, i.e., receptors respond to a single linear feature of the stimulus. Our data support the notion of a division of labor of the active and passive electrosensory systems in weakly electric fishes based on frequency tuning. Future experiments will address the role of central convergence of ampullary input that we expect to lead to higher sensitivity and encoding power of the system.
Assuntos
Potenciais de Ação/fisiologia , Peixe Elétrico/fisiologia , Células Ciliadas da Ampola/fisiologia , Neurônios Aferentes/fisiologia , Animais , Estimulação Elétrica/métodos , Feminino , Células Ciliadas da Ampola/citologia , Masculino , Neurônios Aferentes/citologia , Distribuição AleatóriaRESUMO
Acid-sensing ion channel 2 (ASIC2) plays a role as a mechanorecptor and acid receptor in the peripheral and central nervous systems. However, several recent studies have suggested that ASIC2 is expressed in several organs, in addition to the nervous system. We have examined the expression and distribution of ASIC2 in rat ciliated cells (trachea and oviduct) and stereociliated cells (epididymis, Corti organ, and ampullary crest) by immunohistochemistry and transmission electron microscopy (TEM). Immunohistochemistry revealed that ASIC2 was expressed in both ciliated cells and stereociliated cells, but the localization differed between these cell types. In ciliated cells, ASIC2 was coexpressed with a cilial marker (acetylated tubulin). In stereociliated cells stained with a stereocilial marker (phalloidin), ASIC2 was observed in the cell body. Observation by TEM suggested that ASIC2 expression was present at the apical side of the cilial membrane in ciliated cells and at the apical side of the cell body in stereociliated cells. This study thus indicates that the proton receptor ASIC2 is expressed in both ciliated and stereociliated cells.
Assuntos
Cílios/metabolismo , Canais Epiteliais de Sódio/metabolismo , Células Ciliadas da Ampola/fisiologia , Células Ciliadas Auditivas/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Canais Iônicos Sensíveis a Ácido , Sequência de Aminoácidos , Animais , Cílios/ultraestrutura , Canais de Sódio Degenerina , Epididimo/citologia , Canais Epiteliais de Sódio/genética , Feminino , Células Ciliadas da Ampola/citologia , Células Ciliadas Auditivas/citologia , Masculino , Dados de Sequência Molecular , Proteínas do Tecido Nervoso/genética , Oviductos/citologia , Ratos , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Traqueia/citologiaRESUMO
Histamine-related drugs are commonly used in the treatment of vertigo and related vestibular disorders. Their site and mechanism of action, however, are still poorly understood. To increase our knowledge of the histaminergic system in the vestibular organs, we have investigated the expression of H1 and H3 histamine receptors in the frog and mouse semicircular canal sensory epithelia. Analysis was performed by mRNA reverse transcriptase-PCR, immunoblotting and immunocytochemistry experiments. Our data show that both frog and mouse vestibular epithelia express H1 receptors. Conversely no clear evidence for H3 receptors expression was found.