A common origin of voltage noise and generator potentials in statocyst hair cells

Voltage noise, generator potentials, and hair movements in the Hermissenda statocyst were analyzed. Motile hairs on the cyst's luminal surface moved as rods through +/- 10 degrees Hz when free and at 7 Hz when loaded with the weight of the statoconia (at 120 degrees C). For hair cells oriented opposite to a centrifugal force vector, rotation caused depolarization and increase of voltage noise variance. The depolarizing generator potential and the increase in voltage noise variance were similarly reduced by perfusion with zero external sodium or chloral hydrate. Cooling, perfusion with zero external sodium or chloral hydrate reduced the movement frequencies of the hairs but increased their range of motion. The same treatments reduced voltage noise variance and increased input resistance of the hair cell membrane. The results indicate that voltage noise and hair cell generator potential have a common origin: exertion of force on statocyst hairs by the weight of statoconia. The collision of statoconia with the motile hairs, not the hairs' bending, produces most of the voltage noise.     

Mechanisms that regulate mechanosensory hair cell differentiation

Hair cells of the vertebrate inner ear are mechanosensors that detect sound, gravity and acceleration. They have a specialized cytoskeleton optimized for the transmission of mechanical force. Hair cell defects are a major cause of deafness. The cloning of disease genes and studies of model organisms have provided insights into the mechanisms that regulate the differentiation of hair cells and their cytoskeleton. The studies have also provided new insights into the function of receptors such as integrins and protocadherins, and cytoplasmic proteins such as Rho-type GTPases and unconventional myosins, in organizing the actin cytoskeleton.     

Mechanosensory afferents innervating the swimmerets of the lobster

Feathered hair sensilla fringe both rami of the lobster (Homarus americanus) swimmeret. The sensory response to hair displacement was characterized by recording afferent impulses extracellularly from the swimmeret sensory nerve while deflecting sensilla with a rigidly-coupled probe or controlled water movements. Two populations of hairs were observed: "distal" hairs localized to the distal 1/3 of each ramus and "proximal" hairs near its base. Distal hairs are not innervated by a mechanosensory neuron but instead act as levers producing strain within adjacent cuticle capable of activating a nearby hypodermal mechanoreceptor. Hair deflections of 25 degrees or more are required to evoke an afferent response and this response is dependent on hair deflection direction. The frequency and duration of the afferent discharge evoked are determined by the velocity of hair displacement. Each proximal hair is innervated by a single mechanosensory neuron responding phasically to hair deflections as small as 0.2 degrees in amplitude. Deflection at frequencies up to 5 Hz elicits a single action potential for each hair movement; at higher frequencies many deflections fail to evoke an afferent response. These sensilla, which are mechanically coupled, may be activated by the turbulent flow of water produced by the swimmerets during their characteristic beating movements.     

Sound-induced motions of individual cochlear hair bundles

We present motions of individual freestanding hair bundles in an isolated cochlea in response to tonal sound stimulation. Motions were measured from images taken by strobing a light source at the tone frequency. The tips and bases of hair bundles moved a comparable amount, but with a phase difference that increased by 180 degrees with frequency, indicating that distributed fluid properties drove hair bundle motion. Hair bundle rotation increased with frequency to a constant value, and underwent >90 degrees of phase change. The frequency at which the phase of rotation relative to deflection of the bundle base was 60 degrees was comparable to the expected best frequency of each hair cell, and varied inversely with the square of bundle height. The sharpness of tuning of individual hair bundles was comparable to that of hair cell receptor potentials at high sound levels. These results indicate that frequency selectivity at high sound levels in this cochlea is purely mechanical, determined by the interaction of hair bundles with the surrounding fluid. The sharper tuning of receptor potentials at lower sound levels is consistent with the presence of a negative damping, but not a negative stiffness, as an active amplifier in hair bundles.     

Evoked acoustic oto-emissions: effects of atropine

The Evoked Otoacoustic Emissions (EOE) are a sinusoidal wave complex coming from the contractile properties of the cochlea and particularly of the outer hair cells. This activity is influenced by the centrifugal pathways whose transmitter is acetylcholine. In order to study the effects of the functional block of the cochlea, ten young normal subjects were examined recording the EOE before and ten mins after the i.v. infusion of 1 mg of atropine. The statistical analysis of the results has shown a significant decrease only in EOE appearance threshold in absence of modifications of the saturation level. These data have led us to believe that atropine blocking of the centrifugal pathways causes a disfunction of the outer hair cells that accept less energy to be transduced into a neural stimulus and on the other hand more energy as EOEs.     

Intersensory Interactions in Hermissenda

Hair cells of the Hermissenda statocyst respond to photic stimulation. This response requires the presence of at least one of the two eyes. Two principal hair cell responses to light were observed. The activity of photoreceptors in response to a light step is interrupted during firing of contralateral hair cells. The intersensory interactions between the statocyst and visual pathway underlying these responses were examined with simultaneous intracellular recordings. Evidence is presented that the statocyst of Hermissenda is an important channel for visual information.     

Plant cell growth responds to external forces and the response requires intact microtubules

Microfibril deposition in most plant cells is influenced by cortical microtubules. Thus, cortical microtubules are templates that provide spatial information to the cell wall. How cortical microtubules acquire their spatial information and are positioned is unknown. There are indications that plant cells respond to mechanical stresses by using microtubules as sensing elements. Regenerating protoplasts from tobacco (Nicotiana tabacum) were used to determine whether cells can be induced to expand in a preferential direction in response to an externally applied unidirectional force. Additionally, an anti-microtubule herbicide was used to investigate the role of microtubules in the response to this force. Protoplasts were embedded in agarose, briefly centrifuged at 28 to 34g, and either cultured or immediately prepared for immunolocalization of their microtubules. The microtubules within many centrifuged protoplasts were found to be oriented parallel to the centrifugal force vector. Most protoplasts elongated with a preferential axis that was oriented 60 to 90 degrees to the applied force vector. Protoplasts treated transiently with the reversible microtubule-disrupting agent amiprophos-methyl (applied before and during centrifugation) elongated but without a preferential growth axis. These results indicate that brief biophysical forces may influence the alignment of cortical microtubules and that microtubules themselves act as biophysical responding elements.     

The coding of sound pressure and frequency in cochlear hair cells of the terrapin.

Intracellular recordings have been made from single hair cells in the cochlea of the terrapin, and the site of recording has been verified by injection of a fluorescent dye through the recording electrode. A hair cell gives periodic voltage responses graded with the intensity and frequency of the sound stimulus, and produces the largest response at its characteristic frequency. When small current steps are injected through the recording electrode, the voltage response of the cell exhibits damped oscillations at its characteristic frequency. The results are consistent with the idea that the cochlear frequency selectivity arises in two stages and it is suggested that the second stage resides within the hair cell itself.     

Structural development of sensory cells in the ear

The hair cells of the auditory and balance systems of the inner ear have precise structures and orientations related to function. Hair cells differentiate from a homogenous cell population with the initiation of afferent synaptogenesis and appearance of the apical hair bundle being the first definitive structural sign of hair cell development. The cytoskeletal network then develops and the intercellular membrane junctions become more complex. As auditory function is established in mammalian cochlear hair cells, the lateral membrane acquires certain specializations. Accompanying this there is a change from afferent to efferent innervation of outer hair cells.     

Hair cell regeneration in the avian auditory epithelium

Regeneration of sensory hair cells in the mature avian inner ear was first described just over 20 years ago. Since then, it has been shown that many other non-mammalian species either continually produce new hair cells or regenerate them in response to trauma. However, mammals exhibit limited hair cell regeneration, particularly in the auditory epithelium. In birds and other non-mammals, regenerated hair cells arise from adjacent non-sensory (supporting) cells. Hair cell regeneration was initially described as a proliferative response whereby supporting cells re-enter the mitotic cycle, forming daughter cells that differentiate into either hair cells or supporting cells and thereby restore cytoarchitecture and function in the sensory epithelium. However, further analyses of the avian auditory epithelium (and amphibian vestibular epithelium) revealed a second regenerative mechanism, direct transdifferentiation, during which supporting cells change their gene expression and convert into hair cells without dividing. In the chicken auditory epithelium, these two distinct mechanisms show unique spatial and temporal patterns, suggesting they are differentially regulated. Current efforts are aimed at identifying signals that maintain supporting cells in a quiescent state or direct them to undergo direct transdifferentiation or cell division. Here, we review current knowledge about supporting cell properties and discuss candidate signaling molecules for regulating supporting cell behavior, in quiescence and after damage. While significant advances have been made in understanding regeneration in non-mammals over the last 20 years, we have yet to determine why the mammalian auditory epithelium lacks the ability to regenerate hair cells spontaneously and whether it is even capable of significant regeneration under additional circumstances. The continued study of mechanisms controlling regeneration in the avian auditory epithelium may lead to strategies for inducing significant and functional regeneration in mammals.     

The physical basis of gravity stimulus nullification by clinostat rotation

The question of how rotation on a horizontal axis clinostat removes plants from the influence of the gravitational stimulus is answered. It is shown that appropriate horizontal axis clinostat rotation restricts the fall of intracellular particles to a quasi-circular path such that the position of the particle remains virtually stationary within cells. The displacement of the path of fall, due to centrifugal force, is then considered, and a method of determining the optimal rotation rate is developed from physical principles. This method selects the rotation rate which minimizes the volume of cytoplasm through which particles pass under the joint influence of centrifugal and gravitational forces. With the recognition that single axis clinostats are ineffective with large plants or for long experiments, a new type of clinostat is proposed on which intracellular conditions can be rendered virtually identical to those of plants in satellite free fall regardless of plant size or duration of experiment.     

Intercellular cross-linkages between the stereociliary bundles of adjacent hair cells in the guinea pig cochlea

Summary Hair cells of the guinea pig organ of Corti have been examined using high resolution scanning electron microscopy. In addition to the extensive array of cross-links between the stereocilia of individual hair cells which have been reported previously, we have seen examples of attachments between the stereocilia of both adjacent inner and adjacent outer hair cells. The implications of these observations are discussed.     

Human hair follicle-derived mesenchymal stem cells: Isolation,expansion, and differentiation

Hair follicles are easily accessible skin appendages that protect against cold and potential injuries. Hair follicles contain various pools of stem cells, such as epithelial, melanocyte, and mesenchymal stem cells (MSCs) that continuously self-renew, differentiate, regulate hair growth, and maintain skin homeostasis. Recently, MSCs derived from the dermal papilla or dermal sheath of the human hair follicle have received attention because of their accessibility and broad differentiation potential. In this review, we describe the applications of human hair follicle-derived MSCs (hHF-MSCs) in tissue engineering and regenerative medicine. We have described protocols for isolating hHF-MSCs from human hair follicles and their culture condition in detail. We also summarize strategies for maintaining hHF-MSCs in a highly proliferative but undifferentiated state after repeated in vitro passages, including supplementation of growth factors, 3D suspension culture technology, and 3D aggregates of MSCs. In addition, we report the potential of hHF-MSCs in obtaining induced smooth muscle cells and tissue-engineered blood vessels, regenerated hair follicles, induced red blood cells, and induced pluripotent stem cells. In summary, the abundance, convenient accessibility, and broad differentiation potential make hHF-MSCs an ideal seed cell source of regenerative medical and cell therapy.     

毛囊干细胞研究进展

毛囊干细胞定位在毛囊隆突部,该部位细胞具有其它成体干细胞的共同特性,即慢周期、未分化、自我更新能力及体外增殖能力强等。CD34,K15,K19和Nestin可能作为毛囊干细胞的表面标记。毛囊干细胞在体外可诱导分化为神经元细胞,神经胶质细胞,角化细胞,平滑肌细胞和黑色素细胞等,而在体内（移植后）可分化为神经元、黑色素细胞等。在毛囊干细胞信号调控中涉及到许多的调控信号,主要包括WNT信号、BMP信号和NFATc1等基因的作用。     

Perspectives on hair evolution based on some comparative studies on vertebrate cornification

Hair evolution contributed to the biological success of mammals. Hair origin from synapsid scales is speculative and requires extensive modifications of the morphogenetic process transforming lens-shaped dermis of scales into small dermal papillae in hair. Hair evolution from glands is hypothetical but is supported from studies on the signaling control of hair vs. glandular morphogenesis. Based on immunocytochemical and comparative studies, it is hypothesized that the onion-like organization of hair derived from glandular pegs which central part produced lipids and some keratin. In a following stage, involucrin, trichohyalin, and keratins were produced in the central cells of the gland and formed a solid medulla surrounded by keratinocytes of the inner root sheath. The origin of this protohair was possibly related to increased concentration of beta-catenin and other signaling molecules in epithelial cells following the evolution of a dermal papilla. The latter activated the keratogenic genes, already utilized in cells of the claws, in concentric layers of cells of the glandular peg. Lipidogenic genes were depressed. As new genes evolved in the genome of synapsids, new circular layers of keratinocytes containing specialized hard keratins and keratin-associated proteins were formed around medullary cells. The new keratinocytes probably originated the cortex separating medulla from the external cells that became the inner root sheath. The hypothesis indicates that in a following stage, the medulla was obliterated or replaced by cortical cells while the external part of the cortex formed a cuticular surface due to the different growth rate with inner root sheath cells.     

Neural correlates of associative training in Hermissenda

Hair cells in Hermissenda respond to illumination of the ipsilateral and contralateral eyes. These responses are modified by associative training of the animal. The observed electrophysiological changes appear to result from changes in the photoreceptors' synaptic input to the hair cells.     

Diagnostic value of hair shafts and squamous cells in peritoneal washing cytology

OBJECTIVE: Little attention has been given to hair shafts and squamous cells in peritoneal fluid. To investigate their diagnostic value in peritoneal washing specimens, we reviewed peritoneal washing cytology preparations from 83 cases of ovarian tumors. STUDY DESIGN: We reviewed peritoneal washing specimens and histologic sections of 86 cases of ovarian tumors and tumorous conditions, including 22 teratomas, 16 serous adenocarcinomas, 10 clear cell adenocarcinomas, 9 endometrioid adenocarcinomas, 5 cases of endometriosis, 4 mucinous adenomas, 3 serous cystadenocarcinomas and 17 other tumors. RESULTS: We observed both squamous cells and hair shafts surrounded by inflammatory cells in 5 of the 22 cases of ovarian teratoma. Rupture of an ovarian teratoma was clinically and histologically found in one of the five cases. Hair shafts were not observed in the other tumors or in nonneoplastic conditions. The diameter of hair shafts in peritoneal washing specimens ranged from 10 to 28.8 microns (average, 16.6), and such hair shafts were present within an ovarian teratoma examined histologically. The diameter of hair shafts from six normal adults who were examined as controls ranged from 61.5 to 118.6 microns (average, 89.4). CONCLUSION: Hair shafts and squamous cells surrounded by inflammatory cells in peritoneal washing specimens are a diagnostic clue to ovarian teratoma and can be observed even when rupture of the tumor is not detected clinically or microscopically.     

Hair-cell mechanotransduction and cochlear amplification

In the inner ear, sensory hair cells not only detect but also amplify the softest sounds, allowing us to hear over an extraordinarily wide intensity range. This amplification is frequency specific, giving rise to exquisite frequency discrimination. Hair cells detect sounds with their mechanotransduction apparatus, which is only now being dissected molecularly. Signal detection is not the only role of this molecular network; amplification of low-amplitude signals by hair bundles seems to be universal in hair cells. "Fast adaptation," the rapid closure of transduction channels following a mechanical stimulus, appears to be intimately involved in bundle-based amplification.     

Hair follicular cell/organ culture in tissue engineering and regenerative medicine

Hair follicles are complex organs composed of the dermal papilla (DP), dermal sheath (DS), outer root sheath (ORS), inner root sheath (IRS) and hair shaft. Development of hair follicles begins towards the end of the first trimester of pregnancy and is controlled by epidermal–mesenchymal interaction (EMI), which is a signaling cascade between epidermal and mesenchymal cell populations. Hair grows in cycles of various phases. Specifically, anagen is the growth phase, catagen is the involuting or regressing phase and telogen is the resting or quiescent phase. Alopecia is not life threatening, but alopecia often causes severe mental stress. In addition, the number of individuals afflicted by alopecia patients has been increasing steadily. Currently there are two methods employed to treat alopecia, drug or natural substance therapy and human hair transplantation. Although drug or natural substance therapy may retard the progress of alopecia or prevent future hair loss, it may also accelerate hair loss when the medication is stopped after prolonged use. Conversely, the transplantation of human hair involves taking plugs of natural hair from areas in which occipital hair is growing and transplanting them to bald areas. However, the number of hairs that can be transplanted is limited in that only three such operations can generally be performed. To overcome such problems, many researchers have attempted to revive hair follicles by culturing hair follicle cells or mesenchymal cells in vitro and then implanting them in the treatment area.     

Is there any relationship between decreased AgNOR protein synthesis and human hair loss?

Argyrophilic nucleolar organizing region associated proteins (AgNORs) play roles in cell proliferation and a variety of diseases. We attempted to determine whether decreased NOR protein synthesis causes human hair loss. We studied 21 healthy males who suffered hair loss on the frontal/vertex portion of the head. Hair root cells from normal and hair loss sites were stained for AgNOR. One hundred nuclei per site were evaluated and the AgNOR number and NORa/TNa proportions of individual cells were determined using a computer program. The cells from normal sites had significantly higher AgNOR counts than those from hair loss sites. Also, the cells from the normal sites had significantly higher NORa/TNa than cells from the hair loss sites. In the normal sites, the cells demonstrated more NOR protein synthesis than cells in hair loss sites. Therefore, decreased NOR protein synthesis appears to be related to hair loss in humans.