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PubMed1995

Protein kinase C inhibits human hair follicle growth and hair fibre production in organ culture.

In this study we have used a human hair follicle whole-organ culture system to examine the effects of 12-O-tetradecanoyl-phorbol-13-acetate (TPA), a potent activator of protein kinase C (PKC), on hair follicle growth and hair fibre production. Anagen hair follicles were isolated from human facial skin by microdissection and placed in suspension culture in supplemented Williams E medium. Hair follicle and hair fibre lengths were measured daily using an inverted microscope and cumulative growth values were calculated. Treatment with TPA resulted in a potent, dose-dependent inhibition of total cumulative hair follicle growth (IC50 = 1 nM). Hair follicles grew at a comparable rate for 4 days in the presence or absence of 10 nM TPA, after which growth of TPA-treated follicles ceased while control follicles grew by a further 0.8 mm over the subsequent 6 days. In contrast, 10 nM TPA treatment did not affect hair fibre elongation for a period of 8 days, after which TPA-treated fibre production ceased while control fibres grew by a further 0.79 mm over the subsequent 7 days. Incubation of hair follicles with TPA resulted in a 41% inhibition of hair fibre protein synthesis, as measured biochemically from the incorporation of 3H-leucine using a differential akali extraction method. The inhibitory effect of TPA on follicle growth was partially prevented by preincubation with the selective PKC inhibitor H-7, and almost completely prevented by preincubation with the more potent PKC inhibitor Ro 31-7549. Neither agent alone significantly affected follicle growth at concentrations that reversed the TPA response. These findings indicate that PKC is a negative regulator of hair follicle growth, and suggest that PKC may play a part in the transduction of follicular growth-inhibitory signals.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2001

[Loose anagen hair syndrome: a familial case with fetal hair in meconium].

INTRODUCTION: Loose anagen hair syndrome is a recently described hair disorder. We report a familial case. CASE REPORT: Two sisters were examined, 4 years-old and 8 months old, from a consanguineous marriage. At birth, they presented diffuse alopecia of the scalp; the meconium contained black and silky hair. Clinical examination noted the short, fine hair with easy and painless uprooting. No clinical associated symptoms were observed. The trichogram showed 70 p. 100 of anagen hair and 30 p. 100 of telogen hairs. DISCUSSION: Our familial case is original by this clinical symptom: discharge of probably dystrophic foetal hair in the meconium. Loose anagen hair is characterised by easily pluckable hair. The trichogram confirms the diagnostic. It is composed of anagen hairs (80 to 100 p. 100) devoid of sheaths. The loose anagen hair is usually isolated, but associations have been reported. It may occur in families. The precise pathogenesis and treatment of this hair disorder are not known.

Alopecia↗
PubMed1994

Analysis of a new fluoroquinolone derivative (Q-35) in human scalp hair as an index of drug exposure and as a time marker in hair.

Scalp hair samples were obtained every month for three months after administration from healthy male volunteers who participated in the phase I study of a new antimicrobial fluoroquinolone derivative (Q-35). Hairs were cut into 1 cm long pieces successively from the scalp end. Corresponding pieces of 5 hair strands were dissolved in 1 M NaOH and assessed for Q-35 by HPLC. The drug was detectable in the hairs of all subjects taking either a single (400 mg, n = 6) or repeated oral doses of Q-35 (400 mg/day for 6.5 days, total 2600 mg, n = 6). The hair portions containing the drug were shown in most subjects to move outwards along the hair shafts month by month in proportion to the hair growth rate of about 1 cm/month. Q-35 (600 mg/day) was also given to 6 healthy male volunteers for 6.5 days (total 3900 mg) and hair samples were obtained 1 and 3 months after administration. When Q-35 was analyzed along a single hair shaft, the drug was detectable only in 1-2 consecutive 1 cm long pieces, which were also shown to move outwards along the hair shaft with time. A detailed analysis revealed that the drug was contained only in 2-4 consecutive 2.5 mm long pieces of a single hair collected after 3 months, showing that there was no significant axial diffusion of the drug along the hair shaft with time.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2005

Hair cycle-specific expression of versican in human hair follicles.

BACKGROUND: Versican, a large chondroitin sulfate proteoglycan molecule, is implicated in the induction of hair morphogenesis, the initiation of hair regeneration, and the maintenance of hair growth in mouse species. In contrast, in human hair follicles, the distribution and the roles of versican remains obscure. OBJECTIVES: To elucidate the implication of versican in normal human hair growth. METHODS: Versican expression was examined by in situ hybridization (mRNA) and immunohistochemistry (protein). RESULTS: The results clearly showed specific versican gene expression in the dermal papilla of anagen, which apparently decreased in the dermal papilla of catagen hair follicles. No specific signal was detectable in telogen hair follicles. Consistent with ISH results, versican immunoreactivity was extended over the dermal papilla of anagen hair follicles, and again, this staining diminished in the catagen phase of human hair follicles. Interestingly, versican proteins were deposited outside K15-positive epithelial cells in the bulge throughout the hair cycle. Versican immunoreactivity in the dermal papilla was almost lost in vellus-like hair follicles affected by male pattern baldness. CONCLUSION: Specific expression of versican in the anagen hair follicles suggests its importance to maintain the normal growing phase of human as well as mouse.

Adult↗
PubMed1994

The hair follicular cycle of the cryptothrix mouse and the characteristics of its abnormal hair.

The hair follicular changes of the cryptothrix mutant mouse (crh mouse) were examined sequentially from birth to 365 days of age and the characteristics of the abnormal hair were observed. The homozygous crh mouse had no hair coat on the skin surface during the period of observation, but a small number of fuzzy soft hairs in the black pigmented skin of the anagen phase was seen. Cyclic folliculogenesis, however, was observed histologically in the dermis. The first anagen phase developed at 3 to 4 days of age and lasted until about 15 days of age. The hair follicles then entered the telogen phase, which lasted until about 18 to 32 days of age. Thereafter, the follicular cycles were repeated three times about every 20 days until 90 days of age. This pattern coincided well with the normal hair cyclic pattern reported for the mouse and rat. After 100 days of age, however, alternating anagen and telogen phases formed a striped pattern in the skin, with black bands. These black bands became progressively thinner and shifted anteriorly, showing a wavy pattern. The abnormal hair of the homozygous crh mouse showed separation of the hair medulla due to incomplete trichilemmal keratinization in the internal root sheath. The tips of the hair shafts were folded and collapsed under the epidermis and did not erupt on the skin surface. The hair follicles, however, did not differ from those of heterozygous crh mice. Because the homozygous crh mouse failed to form a complete hair shaft, cyclic folliculogenesis of the epidermis could be easily observed macroscopically without depilation. The homozygous crh mouse may prove useful in evaluating new drugs for hair follicular growth.

Animals↗
PubMed2003

Hair keratin pattern in human hair follicles grown in vitro.

The keratin family includes epithelial (soft) keratins and hair (hard) keratins, and can be divided into acidic type I and basic to neutral type II subfamilies. Recently, nine type I and six type II hair keratin genes have been characterized through the screening of a human PAC library. The expression of these genes in the hair follicle was determined in vivo and a combined catalog of acidic and basic hair keratins was established. In this study, we investigated the expression and localization of most of the human hair keratin members of both types in human hair grown in vitro. We show that in vitro growth of hair follicles for 10 days in complete William's E culture medium did not alter the expression pattern of hair keratins. Similarly to the in vivo situation, each hair keratin was localized in precise and discrete compartments of the follicle, ranging from the matrix to the upper cortex and/or the hair cuticle. This study shows that the increase in length of in vitro grown follicles was accompanied by the proper hair shaft keratinization process. It also shows that hair follicle integrity was maintained in vitro, both in terms of gross morphology and molecular organization despite the complexity of the keratin expression pattern.

Culture Techniques↗
PubMed2003

Characterization of hair follicle antigens targeted by the anti-hair follicle immune response.

Alopecia areata is a common disfiguring hair loss disorder that primarily affects the hair follicle as it enters the prolonged growth phase called anagen. The last few years have yielded an explosion of more rigorously obtained data on the etiology and pathogenesis of this disorder. While a consensus is rapidly building in support of an autoimmune pathogenesis, there are still several enigmatic issues to be resolved. These include the possibility that alopecia areata is really a multientity disorder with causes that are multifactorial. This will have important implications for the research scientist's search for the jigsaw puzzle's largest missing piece--the identification of the target autoantigen(s). There is now much evidence that autoimmune diseases with both T and B cell components have shared target autoantigens/epitopes. It is likely that alopecia areata is similar, as there is now very strong evidence for the generation of autoantibodies as well as autoreactive T cells to hair follicles in the pathogenesis of this disease. The following brief review outlines the progress we have made over the last five to ten years in the characterization of hair follicle antigens targeted by antibodies in alopecia areata. Results of these studies now show that the elicitation of antibodies to hair follicle-specific proteins is a highly conserved phenomenon in all affected species studied to date. Candidate autoantigens that have been identified include the 44/46 kDa hair-specific keratin (expressed in the precortical zone of anagen hair follicles) and trichohyalin (an important intermediate filament-associated protein) expressed in the inner root sheath of the growing hair follicle. Moreover, there is evidence that anti-hair follicle antibodies are modulated during the disease process, can occur before clinically detectable hair loss, and may be reduced in titer during successful treatment. Preliminary data from passive transfer experiments suggest that in some species these antibodies may disrupt hair cycling. We are currently applying a more molecular approach (e.g., cDNA library screening) to identify hair follicle antigens truly associated with the onset of the disorder.

Alopecia Areata↗
PubMed1999

Hair cycle-dependent changes in adrenergic skin innervation, and hair growth modulation by adrenergic drugs.

Skin nerves may exert "trophic" functions during hair follicle development, growth, and/or cycling. Here, we demonstrate hair cycle-related plasticity in the sympathetic innervation of skin and hair follicle in C57BL/6 mice. Compared with telogen skin, the number of nerve fibers containing norepinephrine or immunoreactive for tyrosine hydroxylase increased during the early growth phase of the hair cycle (anagen) in dermis and subcutis. The number of these fibers declined again during late anagen. beta2-adrenoreceptor-positive keratinocytes were transiently detectable in the noncycling hair follicle epithelium, especially in the isthmus and bulge region, but only during early anagen. In early anagen skin organ culture, the beta2-adrenoreceptor agonist isoproterenol promoted hair cycle progression from anagen III to anagen IV. The observed hair cycle-dependent changes in adrenergic skin innervation on the one hand, and hair growth modulation by isoproterenol, accompanied by changes in beta2-adrenoreceptor expression of selected regions of the hair follicle epithelium on the other, further support the concept that bi-directional interactions between the hair follicle and its innervation play a part in hair growth control. This invites one to systematically explore the neuropharmacologic manipulation of follicular neuroepithelial interactions as a novel therapeutic strategy for managing hair growth disorders.

Adrenergic Agents↗
PubMed2001

The catalog of human hair keratins. II. Expression of the six type II members in the hair follicle and the combined catalog of human type I and II keratins.

The human type II hair keratin subfamily consists of six individual members and can be divided into two groups. The group A members hHb1, hHb3, and hHb6 are structurally related, whereas group C members hHb2, hHb4, and hHb5 are rather distinct. Specific antisera against the individual hair keratins were used to establish the two-dimensional catalog of human type II hair keratins. In this catalog, hHb5 showed up as a series of isoelectric variants, well separated from a lower, more acidic, and complex protein streak containing isoelectric variants of hair keratins hHb1, hHb2, hHb3, and hHb6. Both in situ hybridization and immunohistochemistry on anagen hair follicles showed that hHb5 and hHb2 defined early stages of hair differentiation in the matrix (hHb5) and cuticle (hHb5 and hHb2), respectively. Although cuticular differentiation proceeded without the expression of further type II hair keratins, cortex cells simultaneously expressed hHb1, hHb3, and hHb6 at an advanced stage of differentiation. In contrast, hHb4, which is undetectable in hair follicle extracts and sections, could be identified as the largest and most alkaline member of this subfamily in cytoskeletal extracts of dorsal tongue. This hair keratin was localized in the posterior compartment of the tongue filiform papillae. Comparative analysis of type II with the previously published type I hair keratin expression profiles suggested specific, but more likely, random keratin-pairing principles during trichocyte differentiation. Finally, by combining the previously published type I hair keratin catalog with the type II hair keratin catalog and integrating both into the existing catalog of human epithelial keratins, we present a two-dimensional compilation of the presently known human keratins.

Amino Acid Sequence↗
PubMedDate not supplied

Hair analysis for cocaine: the requirement for effective wash procedures and effects of drug concentration and hair porosity in contamination and decontamination.

It has been proposed that issues of external contamination of hair can be resolved by the presence of metabolites. This is true for some drugs in some circumstances. However, even if some metabolites such as cocaethylene are sufficiently definitive to indicate certainty of use, others such as benzoylecgonine can occur as contaminants. In addition, for phencyclidine, only the parent compound is determined. Therefore, effective washing procedures are needed to rule out contamination as the source of the parent or metabolite. The protection provided by cutoffs is also dependent on washing to remove surface contamination, which can range from very little to greater than 20 times the amount in the hair. In cocaine-positive head hair samples from 67 subjects with cocaine-positive urine tests, contamination of positive hair samples ranged from 0.7 to 8009 ng/10 mg hair, demonstrating that analyses of such samples to determine use is meaningless without removal of contamination. Wash procedures have been a focus of this laboratory for many years. In this paper, the effectiveness of our wash procedure was further challenged by application to negative hair (blonde, auburn, brown, and black) contaminated by soaking for 1 h in 1000, 10,000, and 50,000 ng cocaine/mL water. The uptake of the cocaine was approximately linear with increasing concentrations of cocaine in the soaking solutions. By application of the wash criterion, all samples were clearly identified as contaminated (i.e., negative). The effects of hair porosity on uptake of cocaine were also studied with 10 hair samples of all colors. Permed and unpermed samples were soaked in 10,000 ng cocaine/mL for 1 hour. All hair responded to the perm with increased uptake, and all were decontaminated or identified as contaminated (i.e., negative for cocaine use). Porosity, not hair color, determined the rate of penetration of hair by cocaine in solution, and, likewise, washing characteristics were unrelated to hair color.

Cocaine↗
PubMed1995

Immortalized rat whisker dermal papilla cells cooperate with mouse immature hair follicle buds to activate type IV procollagenases in collagen matrix coculture: correlation with ability to promote hair follicle development in nude mouse grafts.

An in vivo nude mouse graft model and an in vitro collagen matrix culture system were used to study interactions of immature hair follicle buds from newborn mice with clonally derived AdE1A-12S-immortalized rat whisker dermal papilla cell lines. Of the 19 available dermal papilla cell lines, four consistently supported good hair follicle development and hair growth in grafts. Seven cell lines were clearly negative in this assay, and the remaining eight cell lines yielded poor to moderate hair growth. As a correlate to in vivo extracellular matrix remodeling accompanying hair follicle development, type IV collagenase activity in the medium from cocultures of dermal papilla cells and hair follicle buds was analyzed by gelatin zymography. Hair follicle buds cultured alone secrete primarily the 92-kDa type IV procollagenase. Cocultivation of hair follicle buds with eight of the dermal papilla cell lines resulted in activation of this proenzyme and activation of the 72-kDa and 92-kDa type IV procollagenases produced by the dermal papilla cells. Seven of these eight dermal papilla cell lines support hair growth in the graft system. In the absence of dermal papilla cells, several growth factors induced activation of the 92-kDa procollagenase secreted by hair follicle buds cultured in serum-free medium: epidermal growth factor, transforming growth factor alpha, acidic fibroblast growth factor, and keratinocyte growth factor. The current working hypothesis is that a) hair follicle epithelial cells interact with dermal papilla cells in coculture by mutual induction of growth factors and cytokines that stimulate the release and activation of matrix remodeling proteases; and b) the ability of dermal papilla cells to interact with hair follicle epithelial cells in this way may be crucial for controlled dermal matrix remodelling during HF development.

Animals↗
PubMed1997

Hair analysis for drugs of abuse. XVIII. 3,4-Methylenedioxymethamphetamine (MDMA) disposition in hair roots and use in identification of acute MDMA poisoning.

Disposition of 3,4-methylenedioxymethamphetamine (MDMA) in hair roots was studied using rats and the hair root samples were evaluated to prove acute MDMA poisoning. The back hair of male pigmented hairy rats (n = 6) was shaved and 5 d later the animals were intraperitoneally administered with acute poisonous doses (20, 40, 60, 80 and 100 mg/kg) of MDMA. Roots of the hairs were then plucked out with a hair nipper 5 min and, 0.5, 1, 2, 6 and 24 h after injection. The hair root samples were, directly or after being washed with detergent, extracted with methanol-5 N HCl (20:1) under ultrasonication in ice-cold water for 4 h. After filtration and evaporation, the residue was derivatized with pentafluoropropionic anhydride and analyzed by GC/MS. From all samples including the 5 min sample, MDMA was detected at high concentrations (up to 156 ng/mg) accompanied by 3,4-methylenedioxyamphetamine (MDA). Some of the animals died within 2 h after administration, but in the surviving rats the MDMA concentrations in the hair roots increased up to 6 h and then slowly decreased until 24 h. The remaining MDMA after washing apparently increased from 13-31% at 0.5 h to 51-83% at 24 h in the surviving rats. These facts show that most of drugs in the hair roots are not yet immobilized in the early stage and are thereafter gradually incorporated into the hair shaft. Increase of the MDMA concentration stopped soon after death of the animal, probably due to the cessation of hair growth. Although the ratios of MDA/MDMA steadily increased over time, those after death plateaued, probably due to the cessation of metabolism after death. It was clearly shown that MDMA is more quickly incorporated into and more firmly retained in hair than methamphetamine (MA) by comparing their disposition in hair roots.

Acute Disease↗
PubMed2005

The Arabidopsis root hair mutants der2-der9 are affected at different stages of root hair development.

Root hairs are an excellent model system to study cell developmental processes as they are easily accessible, single-celled, long tubular extensions of root epidermal cells. In a genetic approach to identify loci important for root hair development, we have isolated eight der (deformed root hairs) mutants from an ethylmethanesulfonate (EMS)-mutagenized Arabidopsis population. The der lines represent five new loci involved in root hair development and show a variety of abnormalities in root hair morphology, indicating that different root hair developmental stages are affected. A double mutant analysis with the short root hair actin2 mutant der1-2 confirmed that the der mutants are disturbed at different time points of root hair formation. Auxin and ethylene are known to be important for trichoblast cell fate determination and root hair elongation. Here, we show that they are able to suppress the phenotype of two der mutants. As the auxin- and ethylene-responsive der mutants are affected at different stages of root hair formation, our results demonstrate that the function of auxin and ethylene is not limited to cell differentiation and root hair elongation but that the two hormones are effective throughout the whole root hair developmental process.

Alleles↗
PubMed1997

The COW1 locus of arabidopsis acts after RHD2, and in parallel with RHD3 and TIP1, to determine the shape, rate of elongation, and number of root hairs produced from each site of hair formation.

Two recessive mutant alleles at CAN OF WORMS1 (COW1), a new locus involved in root hair morphogenesis, have been identified in Arabidopsis thaliana L. Heynh. Root hairs on Cow1- mutants are short and wide and occasionally formed as pairs at a single site of hair formation. The COW1 locus maps to chromosome 4. Root hairs on Cow1- plants form in the usual positions, suggesting that the phenotype is not the result of abnormal positional signals. Root hairs on Cow1- roots begin hair formation normally, forming a small bulge, or root hair initiation site, of normal size and shape and in the usual position on the hair-forming cell. However, when Cow1- root hairs start to elongate by tip growth, abnormalities in the shape and elongation rate of the hairs become apparent. Genetic evidence from double-mutant analysis of cow1-1 and other loci involved in root hair development supports our conclusion that COW1 is required during root hair elongation.

Alleles↗
PubMed2000

Hair analysis for drugs of abuse. Hair color and race differentials or systematic differences in drug preferences?

There is currently a debate in the literature on chemical drug analysis concerning the contribution of biophysical attributes associated with specimens and specimen donors to assay outcome. In recent years this debate has focused on hair analysis, but has in the past also been raised in urinalysis interpretation. In this article we examine several aspects of that controversy. First, we present data regarding the effects of hair color on the distribution of positive hair testing results for three drug classes. We compare these results to negative hair samples from comparable donors. This data is derived from head hair from preemployment donors that was classified according to seven visual color categories. We determined the distribution of colors for hair samples devoid of any of three assayed drugs (amphetamines, cocaine, and cannabinoids). Subsequently, this distribution was compared with the distributions for hairs that had tested positive for amphetamines, cocaine or cannabinoids. We examined a total of 2000 randomly selected samples; 500 negative hair samples and 500 positive samples for each of three drugs: cannabinoids, cocaine, and amphetamine. We also evaluated ethnic/racial factors in relation to positive urinalyses for various ethnic/racial groups. We examined approximately 4000 urine specimens from two different groups, each constituting around 2000 specimens. In addition to ethnicity/race and urinalysis outcome, we also examined the relationship between the hair color distributions of urine donors and the corresponding urinalysis results for the three drug classes. We also compared them to drug-negative samples. Our summary impression is that the observed outcome patterns were largely consistent with differences in drug preferences among the various societal groups. There was little evidence of a pattern attributable to hair color bias alone or selective binding of drugs to hair of a particular color. Likewise, there was no discernible pattern associated with race or ethnicity that would lend support to a "race effect" in drug analysis.

Amphetamines↗
PubMed1998

The incorporation of drugs into hair: relationship of hair color and melanin concentration to phencyclidine incorporation.

Rodents with different hair pigmentation patterns were studied to evaluate the role of melanin in the incorporation of phencyclidine (PCP) into hair. There are two types of melanin in hair and other tissues: eumelanin, a brown-black pigment and pheomelanin, a reddish-yellow pigment. Sprague Dawley (SD; nonpigmented), Dark Agouti (DA; brown), Copenhagen (CP; brown hooded), Long Evans (LE; black hooded), and LBNF1 (deep brown) rats and Swiss-Webster (SW; nonpigmented), C57BL6 (black), and C57BL6 Ay/a (yellow) mice were administered PCP at 10 mg/kg/day for 5 days (n = 5 for each strain). Hair was collected either 14 (rats) or 35 (mice) days (mice) after beginning drug administration and analyzed for PCP, eumelanin, and pheomelanin. PCP concentrations in ng/mg (mean +/- SEM) were as follows: SD, 0.46 +/- 0.13; DA, 12.25 +/- 1.24; CP nonpigmented, 0.12 +/- 0.004; CP pigmented, 9.16 +/- 2.8; LE nonpigmented, 0.66 +/- 0.07; LE pigmented, 21.2 +/- 1.4; LBNF1, 21.64 +/- 3.8; SW, 0.48 +/- 0.36; C57 black, 11.0 +/- 4.03; and C57 yellow, 2.26 +/- 0.55. Eumelanin concentrations in microg/mg (mean +/- SEM) were as follows: DA, 20.50 +/- 1.58; CP pigmented, 19.43 +/- 0.40; LE pigmented, 17.56 +/- 0.61; LBNF1, 27.26 +/- 2.52; C57 black, 37.33 +/- 3.61; and C57 yellow, 1.76 +/- 0.02. Eumelanin was not detected in nonpigmented hair. Pheomelanin concentrations in microg/mg (mean +/- SEM) were as follows: DA, 0.09 +/- 0.00; CP pigmented, 0.20 +/- 0.03; LBNF1, 0.06 +/- 0.01; C57 black, 0.16 +/- 0.05; and C57 yellow, 29.16 +/- 0.97. Pheomelanin was not detected in nonpigmented or LE pigmented hair. These data demonstrate that PCP is incorporated into black hair to a greater extent than yellow or nonpigmented hair. There appears to be a linear relationship between the PCP concentration in hair and the ratio of eumelanin to pheomelanin. Our data suggest that despite variations in PCP concentration because of hair color, they may be normalized by using the ratio of eumelanin to pheomelanin rather than hair weight.

Animals↗
PubMed2007

Atoh1 expression defines activated progenitors and differentiating hair cells during avian hair cell regeneration.

In the avian inner ear, nonsensory supporting cells give rise to new sensory hair cells through two distinct processes: mitosis and direct transdifferentiation. Regulation of supporting cell behavior and cell fate specification during avian hair cell regeneration is poorly characterized. Expression of Atoh1, a proneural transcription factor necessary and sufficient for developmental hair cell specification, was examined using immunofluorescence in quiescent and regenerating hair cell epithelia of mature chickens. In untreated birds, Atoh1 protein was not detected in the auditory epithelium, which is quiescent. In contrast, numerous Atoh1-positive nuclei were seen in the utricular macula, which undergoes continual hair cell turnover. Atoh1-positive nuclei emerged in the auditory epithelium by 15 hr post-ototoxin administration, before overt hair cell damage and supporting cell re-entry into the cell cycle. Subsequently, Atoh1 labeling was seen in 15% of dividing supporting cells. During cell division, Atoh1 was distributed symmetrically to daughter cells, but Atoh1 levels were dramatically regulated shortly thereafter. After cellular differentiation, Atoh1 labeling was confined to hair cells regenerated through either mitosis or direct transdifferentiation. However, Atoh1 expression in dividing progenitors did not necessarily predict hair cell fate specification in daughter cells. Finally, predominant modes of hair cell regeneration varied significantly across the radial axis of the auditory epithelium, with mitosis most frequent neurally and direct transdifferentiation most frequent abneurally. These observations suggest a role for Atoh1 in re-specifying supporting cells and in biasing postmitotic cells toward the hair cell fate during hair cell regeneration in the mature chicken ear.

Animals↗