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Biomedical subjects

J T Corwin

Publications and source records attributed to J T Corwin.

At least 37 records · Page 2Linked to original sources
PubMed1993

The developing organ of Corti contains retinoic acid and forms supernumerary hair cells in response to exogenous retinoic acid in culture.

The mammalian organ of Corti has one of the most highly ordered patterns of cells in any vertebrate sensory epithelium. A single row of inner hair cells and three or four rows of outer hair cells extend along its length. The factors that regulate the formation of this strict pattern are unknown. In order to determine whether retinoic acid plays a role during the development of the organ of Corti, exogenous retinoic acid was added to embryonic mouse cochleae in vitro. Exogenous retinoic acid significantly increased the number of cells that developed as hair cells and resulted in large regions of supernumerary hair cells and supporting cells containing two rows of inner hair cells and up to 11 rows of outer hair cells. The effects of retinoic acid were dependent on concentration and on the timing of its addition. Western blot analysis indicated that cellular retinoic acid binding protein (CRABP) was present in the sensory epithelium of the embryonic cochlea. The amount of CRABP apparently increased between embryonic day 14 and postnatal day 1, but CRABP was not detectable in sensory epithelia from adults. A retinoic acid reporter cell line was used to demonstrate that retinoic acid was also present in the developing organ of Corti between embryonic day 14 and postnatal day 1, and was also present in adult cochleae at least in the vicinity of the modiolus. These results suggest that retinoic acid is involved in the normal development of the organ of Corti and that the effect of retinoic acid may be to induce a population of prosensory cells to become competent to differentiate as hair cells and supporting cells.

Animals↗
PubMed1993

Replacement of lateral line sensory organs during tail regeneration in salamanders: identification of progenitor cells and analysis of leukocyte activity.

It has been proposed that supporting cells may be the progenitors of regenerated hair cells that contribute to recovery of hearing in birds, but regeneration is difficult to visualize in the ear, because it occurs deep in the skull. Hair cells and supporting cells that are comparable to those in the ear are present in lateral line neuromasts, and in axolotl salamanders these cells are accessible to microscopic observation in vivo. After amputation of a segment of the tail that contains neuromasts, cells from the posteriormost neuromast on the tail stump divide rapidly and form a migratory regenerative placode. The cells of the regenerative placode represent a lineage that eventually produces both hair cells and supporting cells in replacement neuromasts. We sought to identify the progenitors of the regenerative placode by using differential interference contrast microscopy combined with time-lapse video recording in living axolotl salamanders. In response to amputation, the mantle-type supporting cells at the posteroventral edge of the neuromast that is nearest to the wound increased their frequency of cell division, and gave rise to the first cells of the placode. The increase in mitotic activity of mantle-type supporting cells was accompanied by an unexplained decrease in the frequency of divisions in the same neuromast's population of internal supporting cells. The time-lapse records suggested that the changes in the mitotic activity of supporting cells might have been linked to the presence of phagocytic leukocytes in the vicinity of the neuromast that was nearest to the wound. Leukocytes were evenly distributed around control neuromasts, but during regeneration leukocyte activity increased significantly in the vicinity of the posterior half of the posteriormost neuromast. The redistribution of leukocytes occurred early in the regenerative response, but a causal role for the leukocytes has not been conclusively established. It is possible that the leukocytes could contribute to the formation of the regenerative placode at that location by breaking down the glycocalyx that ensheaths the outermost cells of the neuromast, or through the secretion of mitogenic growth factors.

Ambystoma mexicanum↗
PubMed1992

Regeneration in the auditory system.

The auditory organs of birds and mammals normally stop producing sensory hair cells during embryonic development, so loss of those cells later in life results in hearing deficits that have been considered irreversible. In contrast to this, the ears of some fish and amphibians produce hair cells continuously throughout life and even increase in sensitivity. The lateral line organs in the skin of fish and aquatic amphibians also contain hair cells and have long been known to be replaceable through regeneration. Recently, it was discovered that after acoustic trauma or antibiotic poisoning, injured hair cells in the mature auditory organs of birds also could be replaced through regeneration. This is especially notable because it occurs in populations of cells that are mitotically quiescent in undamaged ears. More recent investigations have focused on identifying the cells that give rise to new hair cells during regeneration. In the lateral line organs of salamanders, time-lapse video microscopy has revealed that surviving supporting cells divide to give rise to progeny that can differentiate either as hair cells or as supporting cells. Definitive identification of the progenitors of regenerated hair cells in the avian cochlea awaits further investigation, but evidence that points to two possible candidate cell types is discussed.

Animals↗
PubMed1992

Maturation of kinocilia in amphibian hair cells: growth and shortening related to kinociliary bulb formation.

New hair cells are added to the amphibian sacculus throughout life, primarily at its outer edge. The stereociliary bundles near that edge are heterogeneous, but eventually develop the more homogeneous morphology of the overwhelming majority of mature cells near the center of the epithelium. During their development the kinocilium grows and a kinociliary bulb forms. It has been proposed that initial elongation of the kinocilium is followed by shortening, and that the bulb may form during shortening. To test those hypotheses, amphibian sacculi were examined by scanning electron microscopy and the length of the kinocilium, the width of the kinociliary bulb, and the length of the tallest stereocilia were measured for 159 hair cells. The length of the tallest stereocilia on each hair cell was used as an indicator of the relative maturity of that cell, so that changes in the structure of each cell's kinocilium could be related to that cell's stage of development. Results indicate that initial elongation of the kinocilium is followed by shortening. Kinociliary bulbs first appear and increase in volume as shortening proceeds. These findings support the hypotheses. Models are proposed to explain how the formation of the bulb could result from depolymerization of apical cytoskeletal elements, and how kinocilium growth and shortening may contribute to hair bundle reorientation in the developing ear.

Animals↗
PubMed1991

Hair cell regeneration: the identities of progenitor cells, potential triggers and instructive cues.

Hair cells are produced and accumulate in the ears of fish and amphibians as they grow during postembryonic life; hair cell regeneration occurs in lateral line organs in those groups and in the cochlea in birds. Continuous time-lapse microscopy has directly demonstrated that supporting cells divide to give rise to hair cells during regeneration in lateral line neuromasts. Supporting cells also appear to give rise to hair cells during regeneration in the avian ear, but additional cell types have been proposed as hair cell progenitors. Alternative interpretations of current evidence are discussed in relation to the possibility that supporting cells may be the common progenitor in all cases of hair cell regeneration. The regenerative proliferation of hair cells in birds occurs in populations of cells that are mitotically quiescent in undamaged ears. Evidence suggests that the extrusion of damaged hair cells and the breaking of intercellular junctional adhesions may be a trigger for regenerative proliferation. The potential triggering influence of phagocytes is also discussed. The differentiation of replacement cells during regeneration in the cochlea may be regulated by surface interactions between cells. A model that could account for the reconstitution of the mosaic pattern of hair cells and supporting cells is proposed.

Animals↗
PubMed1991

Stereociliary bundles reorient during hair cell development and regeneration in the chick cochlea.

We have examined changes in the orientation of stereociliary bundles of hair cells in the cochlear sensory epithelium that occur during normal embryonic development and during the regeneration of hair cells that follows acoustic trauma. At the time when hair cell surfaces become recognizable in the embryonic cochlea, the bundles of stereocilia exhibit a range of orientations, as indicated by the position of the kinocilium and later, by the location of the tallest row of stereocilia. With time, the orientations of bundles on neighboring hair cells become more uniform, a condition that is maintained in the adult. Changes in stereocilia orientation are also observed during the regeneration of hair cells after acoustic trauma. When new hair cells first differentiate at sites of trauma in the recovering sensory epithelium, their stereociliary bundles are not uniformly oriented. Then as the cells mature over a period of days, the bundles become aligned both with the neighboring bundles in the region of the previous lesion and with the pre-existing bundles that surround the site of regeneration. We conclude that the stereociliary bundles of hair cells are reorienting as the cells differentiate. A common mechanism may guide reorientation both during embryonic development and during regeneration. Observations in living cochleae indicate that differentiating stereociliary bundles establish asymmetric linkages to the extracellular matrix of the developing tectorial membrane. During the growth of the tectorial membrane, its progressive extension across the surface of the sensory epithelium may exert traction forces through those asymmetric linkages that pull the bundles of the hair cells into uniform alignment.

Animals↗
PubMed1990

Selective labeling of sensory hair cells and neurons in auditory, vestibular, and lateral line systems by a monoclonal antibody.

This study reports that zn-1, a monoclonal antibody, labels hair cells but not supporting cells in the inner ear and the lateral line of the axolotl salamander, Ambystoma mexicanum. Zn-1 immunocytochemically labels the cytoplasm and stereocilia of mature hair cells in the sacculus, in the utriculus, and in the mechanoreceptive neuromast organs of the lateral line. Lower levels of labeling mark newly formed hair cells in the periphery of the sacculus and in regenerating neuromasts. Zn-1 also selectively labels neuronal processes and perikarya in the lateral line nerves and ganglia and the VIIIth cranial nerve and ganglion. Processes and perikarya are labeled by zn-1 in the dorsolateral medulla oblongata, at sites of termination of the afferent octaval and lateral line neurons. Western blot analysis revealed that zn-1 labels one or more proteins with molecular weights of 80 and 160 kDa. The identity of these protein bands remains to be determined. The presence of a specific epitope expressed in both hair cells and neurons, but not in supporting cells, in the vestibular and auditory epithelia of the ear and in the mechanoreceptive neuromasts of the lateral line suggests shared cytogenetic heritages. These findings are consistent with a close evolutionary relationship between otic and lateral line senses, such as that inherent to the theoretical evolutionary scheme outlined in van Bergeijk's "acousticolateralis hypothesis." The protein recognized by zn-1 is as yet unidentified, but its conservative evolution suggests that it may serve an important function in the statoacoustic and lateral line systems.

Afferent Pathways↗
PubMed1990

Regenerated hair cells can originate from supporting cell progeny: evidence from phototoxicity and laser ablation experiments in the lateral line system.

The mechanisms that lead to the production of sensory hair cells during regeneration have been investigated by using 2 different procedures to ablate preexisting hair cells in individual neuromast sensory epithelia of the lateral line in the tails of salamanders, then monitoring the responses of surviving cells. In one series of experiments, fluorescent excitation was used to cause the phototoxic death of hair cells that selectively take up the pyridinium dye DASPEI. In the other experiments, the ultraviolet output of a pulsed neodymium-YAG laser was focused to a microbeam through a quartz objective lens in epi-illumination mode and used to selectively kill individual unlabeled hair cells while the cells were simultaneously imaged by transmitted light DIC microscopy. Through observation of the treated neuromasts in vivo, these experiments demonstrated that mature sensory epithelia that have been completely depleted of hair cells can still generate new hair cells. Preexisting hair cells are not necessary for regeneration. Immediately after the ablations the only resident cells in the sensory epithelia were supporting cells. These cells were observed to divide at rates that were increased over control values, and eventually those cell divisions gave rise to progeny that differentiated as hair cells, replacing those that had been killed. Macrophages were active in these epithelia, and their phagocytic activity had a significant influence on the standing population of cells. The first new hair cells appeared 3-5 d after the treatments, and additional hair cells usually appeared every 1-2 d for at least 2 weeks. We conclude that the fate of the progeny produced by supporting cell divisions is plastic to a degree, in that these progeny can differentiate either as supporting cells or as hair cells in epithelia where hair cells are missing or depleted.

Ambystoma↗
PubMed1989

Development of location-specific hair cell stereocilia in denervated embryonic ears.

The developmental mechanisms that allow physiological coding of acoustic pitch have remained unexplained. Cochlear hair cells that have different structures respond to different sound frequencies and synapse with neurons that project to different locations in the brain. How do these hair cells develop appropriate structures, and how are the connections between specific hair cells and the neurons that code for their pitch sensitivities matched? We have investigated one aspect of this by denervating embryonic chicken ears, before the time of hair cell production, and then transplanting them to the aneural chorioallantoic membrane of host embryos where they have continued to develop. We report that vestibular and auditory hair cell phenotypes differentiate appropriately and that correct gradients of hair cell structural phenotypes, as expressed in stereocilia bundles, develop in the cochleae of these denervated ears. Therefore, the normal development of gradients in hair cell stereocilia properties must be controlled by location-specific cues originating in the ear itself. Neuronally directed modification of target cell phenotypes is not required for the quite specific phenotype development represented by the stereocilia bundles of individual hair cells and the connectional matching in the numerous distinct peripheral information lines of the auditory system.

Animals↗
PubMed1989

Cell production in the chicken cochlea.

In the chicken cochlea, the structural features of the cilia bundles of individual hair cells vary systematically along the length of the sensory epithelium. As a first approach to understanding the developmental mechanisms that underlie this precise arrangement of structurally distinct hair cells, the spatiotemporal pattern of the terminal mitoses of their precursor cells was investigated by administering 3H-thymidine, a radioactive precursor to DNA. This demonstrated that the first hair cells were produced during the sixth day of incubation and formed a longitudinal band that extended along most of the length of the sensory epithelium. The epithelium grew further through appositional addition of hair cells at the edges of this first band of cells, and the hair cell addition process expanded into the surrounding areas during the next 3 days. By the ninth day of incubation all the hair cells in the sensory epithelium except for those at the peripheral edges in the distal (apex) portion had been produced through terminal mitoses. Our results have demonstrated that hair cells that have similar stereocilia phenotypes do not all leave the mitotic cycle at the same time.

Animals↗
PubMed1988

Regeneration of sensory hair cells after acoustic trauma.

Any loss of cochlear hair cells has been presumed to result in a permanent hearing deficit because the production of these cells normally ceases before birth. However, after acoustic trauma, injured sensory cells in the mature cochlea of the chicken are replaced. New cells appear to be produced by mitosis of supporting cells that survive at the lesion site and do not divide in the absence of trauma. This trauma-induced division of normally postmitotic cells may lead to recovery from profound hearing loss.

Animals↗
PubMed1985

Auditory neurons expand their terminal arbors throughout life and orient toward the site of postembryonic hair cell production in the macula neglecta in elasmobranchs.

The population of sensory hair cells in the macula neglecta auditory epithelium in skates increases from 500 to more than 3,000 postembryonically, but during the same time period the number of neurons innervating the epithelium changes by a much smaller amount, if at all. Morphometric analyses of the peripheral terminal arbors of these neurons demonstrate that the arbors expand in area through intussusceptive growth, so that each neuron contacts more hair cells as the epithelium grows by appositional addition of new hair cells at its outer edge. The synaptic contacts that these neurons make with hair cells may not be permanent. Many of the neurons that innervate the growing macula appear to shift their terminal arbors, breaking synaptic contacts with older hair cells in the center of the sensory epithelium as they branch to form new contacts with younger hair cells that are located in the periphery of the epithelium. Over 80% of the terminal branches of these auditory neurons are directed toward the outer edge of the macula, the site where new hair cells are produced. This suggests that the growth cones of these continually growing neurons are guided to newly produced hair cells by an active attraction mechanism.

Aging↗
PubMed1985

Perpetual production of hair cells and maturational changes in hair cell ultrastructure accompany postembryonic growth in an amphibian ear.

Sensory hair cells are produced in the ears of birds and mammals only during early development, so that a programmed termination of hair cell proliferation leaves adult birds and mammals susceptible to irreversible deafness and balance disorders. This study reports that this is not an inherent feature of hair cells and is not shared through all the vertebrate classes. In toads (Bufo marinus) hair cells accumulate throughout life, increasing in the sacculus from approximately 400 cells at metamorphosis to more than 1600 in adulthood. In both embryonic and postembryonic ears new hair cells have been identified by scanning electron microscopy and through uptake of radioactively labeled thymidine. In the otic vesicle of postneurulation embryos there is a single primordial sensory epithelium that contains approximately 100 hair cells. Scanning electron microscopy has demonstrated that these newly formed hair cells all have stereocilia bundles that are shorter than 1.5 micron, whereas the majority of hair cells in postembryonic ears have stereocilia bundles that are at least 3 micron long. In the postembryonic sacculus the proliferation of hair cells never appears to cease, since newly produced hair cells identified by their short stereocilia have been found in a distinct peripheral growth zone at the edge of the sensory epithelium even in specimens from the oldest 1% of natural populations. This peripheral growth zone is also the site of the most frequent labeling of newly synthesized DNA in hair cells. It appears that the postembryonic enlargement of the toad sacculus occurs primarily through appositional addition of new hair cells at its edge, with few hair cells added within the existing structure of the epithelium.

Animals↗
PubMed1983

Postembryonic growth of the macula neglecta auditory detector in the ray, Raja clavata: continual increases in hair cell number, neural convergence, and physiological sensitivity.

Quantitative scanning electron microscopy in an age series demonstrated that the macula neglecta auditory epithelium of the ray, Raja clavata, produces and accumulates sensory cells perpetually at 1-3 cells/day, so that the total increases from approximately 500 cells at birth to 6,000 at 7 years of age. The shape of the macula also changes with growth, and changes in the marginal zones of small and intermediate size hair cells are consistent with this differential growth and their proposed role as hair cell production sites. The neurons contacting the epithelium do not increase in number as animals age; instead they hypertrophy, increasing axon diameter and terminal field size. A hypothetical double-gradient interaction between the growing nerves and new hair cells is proposed to explain the development of synaptic connections and the continual production of individually oriented, functional hair cells. Electrophysiological recordings from the neurons demonstrated best sensitivities between 40 Hz and 200 Hz, directional receptive fields, and little or no effect of changes in the ear's position relative to gravity. The convergence ratio from sensory cells to neurons increases because of their unequal patterns of growth, and physiological sensitivity improves 500-fold and more as these animals age. These results contrast with current information on mammalian ears, where it appears that sensory cells are not produced at any time after birth.

Animals↗
PubMed1982

Auditory centers in the elasmobranch brain stem: deoxyglucose autoradiography and evoked potential recording.

Elasmobranchs are sensitive to low frequency sound, and electrophysiological studies have demonstrated acoustic responses from the ear. Five primary projections from the ear to the medulla have been found, but individually they could not be identified with either the auditory or the equilibrium modality since they originate in a mixed nerve. Metabolic mapping in the brain of the thornback guitarfish with [14C]2-deoxyglucose autoradiography and acoustic stimulation provided tentative identifications of acoustic centers in cell plate X of the medial octavolateralis nucleus, the anterior octaval nucleus, the nucleus of the lateral lemniscus, and the ventromedial division of the lateral mesencephalic nucleus. Evoked potential recordings confirmed acoustic activity in those sites and additionally in the reticular formation, and the lateral granule cell mass of the auricle. In tests in the mesencephalon the evoked potential disappeared within the range of elasmobranch behavioral thresholds and when the eighth nerves were cut, but was not changed when all 4 lateral line nerves were cut. The identified acoustic centers resemble those found in auditory lemniscal pathways in mammals and other tetrapods, but the most recent ancestor common to elasmobranchs and tetrapods lived 400 million years ago. Therefore, a basic auditory lemniscal pathway may be a longstanding feature of the vertebrate brain.

Animals↗
PubMed1982

The auditory brain stem response in five vertebrate classes.

In representative elasmobranchs, osteichthyans, amphibians, reptiles and birds, average evoked potentials in response to acoustic clicks and tone bursts were recorded intracranially, but outside the brain, or extracranially. Controls against artifacts and tests after transections show that these potentials conform to criteria for auditory brain stem responses (ABRs). Brief waves in a 10-15 msec sequence originate successively in the eighth nerve, medulla and midbrain; there is little contribution to the latter waves from the lower levels. This response pattern appears to be consistent within each species and is similar to that extensively studied in mammals. Some of its features are remarkably alike in all the vertebrate classes tested, implying a generality in the existence of a subset of auditory neurons at several brain levels that are highly synchronous in activity, even after several synapses, and geometrically oriented to add their macroscopic, open, dipole fields. The intensity, repetition rate and the power spectrum of the click stimuli have little effect on the ABR pattern, except when the peak energy is in the low frequency range. In the range below ca. 700 Hz frequency content has a considerable effect; lower frequencies broaden certain waves. Cooling has marked and differential effects on component processes. Reversing click phase, e.g. from initial compression to initial rarefaction, can show no effect or any of several effects, depending on the species. Tone bursts evoke onset ABRs and in some cases after a transitional period a sustained frequency following response. The ABR resembles a click evoked potential even when stimulus rise time is slow. Background tones of particular frequency are most efficient in masking click evoked ABRs; white noise is less efficient. The ABR should be useful in neuroethology since it can be studied without invading the brain. It can tell that the brain is sensitive to a sound. In an immobilized animal it can be recorded in a single sweep, or it can be averaged from an awake tethered animal. It shows good sensitivity and at least some correspondence with behavioral measures of hearing.

Acoustic Stimulation↗
PubMed1981

Postembryonic production and aging in inner ear hair cells in sharks.

In many animals the sensory hair cells of the inner ear are ultrastructurally variable within individual epithelia. This variation has been hypothetically related to both the function and the age of the individual cells. In this study, growth-related changes in hair cell populations were examined in the macula neglecta sensory epithelia of juvenile and adult sharks. Scanning electron microscopy demonstrated that more than 80% of the 200,000 hair cells in the adult's macula negecta are produced postembryonically. Tritiated thymidine autoradiography and histological descriptions of the hair cells in this sound detector indicate that new sensory cells are produced in growth zones at the edges of the epithelia. The hair cells in those zones have small cell bodies, small and heterogeneous cilia complexes, and associations with small numbers of particularly thin nerve terminals. Their cytological features and their sparse innervation contrast with the features of the more numerous central cells in each epithelium, but appear to resemble the published descriptions of embryonically developing hair cells. Thus, a germinal zone at the leading edge of sensory epithelium growth appears to persist into adult life in sharks. Published reports reinterpreted in light of this evidence suggest that such hair cell population growth may be expected in other anamniotes and that latent growth zones might persist in the ears of amniotes.

Aging↗