Kif3a regulates planar polarization of auditory hair cells through both ciliary and non-ciliary mechanisms

Auditory hair cells represent one of the most prominent examples of epithelial planar polarity. In the auditory sensory epithelium, planar polarity of individual hair cells is defined by their V-shaped hair bundle, the mechanotransduction organelle located on the apical surface. At the tissue level, all hair cells display uniform planar polarity across the epithelium. Although it is known that tissue planar polarity is controlled by non-canonical Wnt/planar cell polarity (PCP) signaling, the hair cell-intrinsic polarity machinery that establishes the V-shape of the hair bundle is poorly understood. Here, we show that the microtubule motor subunit Kif3a regulates hair cell polarization through both ciliary and non-ciliary mechanisms. Disruption of Kif3a in the inner ear led to absence of the kinocilium, a shortened cochlear duct and flattened hair bundle morphology. Moreover, basal bodies are mispositioned along both the apicobasal and planar polarity axes of mutant hair cells, and hair bundle orientation was uncoupled from the basal body position. We show that a non-ciliary function of Kif3a regulates localized cortical activity of p21-activated kinases (PAK), which in turn controls basal body positioning in hair cells. Our results demonstrate that Kif3a-PAK signaling coordinates planar polarization of the hair bundle and the basal body in hair cells, and establish Kif3a as a key component of the hair cell-intrinsic polarity machinery, which acts in concert with the tissue polarity pathway.     

Melanocyte stem cells: a melanocyte reservoir in hair follicles for hair and skin pigmentation

Most mammals are coated with pigmented hair. Melanocytes in each hair follicle produce melanin pigments for the hair during each hair cycle. The key to understanding the mechanism of cyclic melanin production is the melanocyte stem cell (MelSC) population, previously known as 'amelanotic melanocytes'. The MelSCs directly adhere to hair follicle stem cells, the niche cells for MelSCs and reside in the hair follicle bulge-subbulge area, the lower permanent portion of the hair follicle, to serve as a melanocyte reservoir for skin and hair pigmentation. MelSCs form a stem cell system within individual hair follicles and provide a 'hair pigmentary unit' for each cycle of hair pigmentation. This review focuses on the identification of MelSCs and their characteristics and explains the importance of the MelSC population in the mechanisms of hair pigmentation, hair greying, and skin repigmentation.     

Essential roles of BMPR-IA signaling in differentiation and growth of hair follicles and in skin tumorigenesis

Hair differentiation and growth are controlled by complex reciprocal signaling between epithelial and mesenchymal cells. To better understand the requirement and molecular mechanism of BMP signaling in hair follicle development, we performed genetic analyses of bone morphogenetic protein receptor 1A (BMPR-IA) function during hair follicle development by using a conditional knockout approach. The conditional mutation of Bmpr1a in ventral limb ectoderm and its derivatives (epidermis and hair follicles) resulted in a lack of hair outgrowth from the affected skin regions. Mutant hair follicles exhibited abnormal morphology and lacked hair formation and pigment deposition during anagen. The timing of the hair cycle and the proliferation of hair matrix cells were also affected in the mutant follicles. We demonstrate that signaling via epithelial BMPR-IA is required for differentiation of both hair shaft and inner root sheath from hair matrix precursor cells in anagen hair follicles but is dispensable for embryonic hair follicle induction. Surprisingly, aberrant de novo hair follicle morphogenesis together with hair matrix cell hyperplasia was observed in the absence of BMPR-IA signaling within the affected skin of adult mutants. They developed hair follicle tumors from 3 months of age, indicating that inactivation of epidermal BMPR-IA signaling can lead to hair tumor formation. Taken together, our data provide genetic evidence that BMPR-IA signaling plays critical and multiple roles in controlling cell fate decisions or maintenance, proliferation, and differentiation during hair morphogenesis and growth, and implicate Bmpr1a as a tumor suppressor in skin tumorigenesis.     

Preferential expression of transient potassium current (IA) by 'short' hair cells of the chick's cochlea

We have made a comparative study of the membrane properties of tall and short hair cells isolated from a selected region of the chick's cochlea. Tall hair cells are analogous to inner cochlear hair cells of mammals, and like those, are presynaptic to the majority of afferent neurons in the cochlea. Short hair cells, like mammalian outer hair cells, are the postsynaptic targets of efferent neurons that inhibit the cochlea. Voltage-clamp recordings have revealed that short hair cells have an inactivating potassium (K) current, IA, whereas tall hair cells have little or none. Short hair cells are also sensitive to the cholinergic agonist carbachol, whereas tall hair cells are not. This pattern is in accord with the selective distribution of efferent cholinergic synapses in the cochlea. Although IA is completely inactivated at the resting potential of the short hair cells, cholinergic agonists can hyperpolarize these cells by as much as 30 mV. This hyperpolarization removes inactivation and allows IA to modulate subsequent voltage-dependent processes in short hair cells. It is concluded that IA could increase the high frequency response of the hair cell by decreasing membrane resistance and thus the membrane time constant after inhibition. This will be of particular importance to cochlear function if short hair cells produce voltage-dependent movements, as do mammalian outer hair cells.     

Racial hair: the persistence and resistance of a category

This article analyses how hair and race are entangled both within anthropology and in the commercial world of the billion-dollar global market for human hair. Focusing in particular on detached hair, it explores the recurring dynamic through which hair is racialized, on the one hand, and resists racialization, on the other. This process is traced in three interrelated contexts, the roots of which are embedded in historical conditions of domination and oppression. The first is that of nineteenth- and early twentieth-century physical anthropology, when hair was thought to provide a key to racial distinctions. The second refers to contemporary black hair cultures in which hair is racialized both in the marketplace, where it is advertised through ethnic signifiers, and in the natural hair movement, which relies on ideas of authenticity based on biological differences. The third context is that of factories in China, where items such as ‘Brazilian’ hair extensions and ‘Afro’ wigs are physically manufactured through combinations of hair and labour that confound ethnic, racial, and national boundaries. By shifting attention to the materiality of hair, the article highlights the enduring materiality of race, exposing its shape-shifting qualities and persistent ideologies and providing a unique angle onto the dynamics of nature-culture articulations.     

Proteins of normal hair and of cysteine-deficient hair from mentally retarded siblings

1. S-Carboxymethylkerateines extracted from normal hair can be fractionated into high-sulphur and low-sulphur proteins similar to those obtained from sheep's wool. Normal human hair gives a major high-sulphur protein of higher molecular weight and S-carboxymethylcysteine content than any isolated from normal sheep's wool. 2. The proteins from cystine-deficient hair can also be divided into high-sulphur and low-sulphur proteins. There is a lower proportion of high-sulphur protein in cystine-deficient hair than in normal hair. 3. The high-sulphur proteins from cystine-deficient hair have an abnormal amino acid composition and in particular are lower in S-carboxymethylcysteine content than the corresponding proteins from normal hair. New components are present and the content of very high-sulphur proteins of high molecular weight is much decreased. The low-sulphur proteins of cystine-deficient hair are probably also deficient in S-carboxymethylcysteine. 4. The proteins of cystine-deficient hair probably resemble those in the normal hair root, except that disulphide-bridge formation has occurred.     

Correction of the cornrow hair transplant and other common problems in surgical hair restoration

Hair on a man's head is an important emblem of health, youth, and vitality. As in all areas of cosmetic surgery, the refinements of surgical technique and instrumentation have improved the results of hair transplantation. The state of the art in hair grafting today produces a result that is undetectable as being a surgical hair transplant. Many earlier techniques of plug hair transplantation are not aesthetically acceptable by today's standards. This is especially true in the face of progressive hair loss, which can unmask previously camouflaged cornrow plugs. A technique to reduce the plugs and recycle the grafts into smaller grafts is described. The recycled hair grafts can be combined with scalp lifting, scalp reductions, and occipital harvesting of grafts to improve the results of cornrow appearing hair transplants and other problems of surgical hair restoration.     

The structure of a hair mechanoreceptor in the antennule of crayfish (Crustacea)

Summary In this study we examine the fine structure of mechanosensory hairs in the antennule of crayfish. The sensory hair is a stiff shaft with feather-like filaments. The hair's base is a large expansion of membrane which allows the hair shaft to deflect. The sensory transducing elements are located far from the hair, but are coupled mechanically with the hair shaft by a fine extracellular chorda. The sensory element is a type of scolopidium which consists of a scolopale cell and three sensory cells with a 9 + 0 type ciliary process.This type of scolopidium is characteristic of the chordotonal organ that has no cuticular structure on the surface of the exoskeleton. In this crustacean hair receptor, the deflection of the cuticular hair is transmitted through the chorda to the scolopidium which is a tension-sensitive transducer. The present study reveals that the mechanosensory hair of decapod crustaceans is a chordotonal organ accompanied by a cuticular hair structure. We also discuss comparative aspects of cuticular and subcuticular chordotonal organs in arthropods.     

Notch1 is essential for postnatal hair follicle development and homeostasis

Notch genes encode evolutionarily conserved large, single transmembrane receptors, which regulate many cell fate decisions and differentiation processes during fetal and postnatal life. Multiple Notch receptors and ligands are expressed in both developing and adult epidermis and hair follicles. Proliferation and differentiation of these two ectodermal-derived structures have been proposed to be controlled in part by the Notch pathway. Whether Notch signaling is involved in postnatal hair homeostasis is currently unknown. Here, we investigate and compare the role of the Notch1 receptor during embryonic hair follicle development and postnatal hair homeostasis using Cre-loxP based tissue specific and inducible loss-of-function approaches. During embryonic development, tissue-specific ablation of Notch1 does not perturb formation and patterning of hair follicle placodes. However, Notch1 deficient hair follicles invaginate prematurely into the dermis. Embryonic as well as postnatal inactivation of Notch1 shortly after birth or in adult mice results in almost complete hair loss followed by cyst formation. The first hair cycle of Notch1 deficient mice is characterized by shortened anagen and a premature entry into catagen. These data show that Notch1 is essential for late stages of hair follicle development during embryogenesis as well as for post-natal hair follicle development and hair homeostasis.     

The patchwork mouse phenotype: implication for melanocyte replacement in the hair follicle.

Mice homozygous for the recessive patchwork (pwk) mutation are characterized by a variegated pigment pattern with a mixture of unpigmented and normally pigmented hairs. The pigmented hair bulbs contain functional melanocytes. By contrast, the unpigmented hair bulbs contain no melanocytes. This lack results from the death of melanoblasts in the hair follicle at the end of embryogenesis. Here, we report that melanoblasts and melanocytes are found in the epidermis of pwk/pwk mice. Furthermore, these epidermal pigment cells are able to colonize new hair follicles after skin wounding. Despite the presence of epidermal pigment cells with a colonization potential, a follicle that had produced an unpigmented hair produces a new unpigmented hair during the successive hair growth cycles. This hair color continuity is also true for the pigmented hair follicles. Thus, in normal conditions, the hair acts as an independent functional unit as regards its pigment cells population.     

Simulation of marked root hair curling in Rhizobium-legume symbiosis

The soil bacterium Rhizobium infects its leguminous host plants in temperate regions of the world mostly by way of the growing root hairs. Root hair curling is a prerequisite for root hair infection, although sidelong root hair infections occasionally have been observed. The processes underlying Rhizobium -induced root hair curling are unknown.
Computer simulation of root hair growth indicates that one-sided tip growth inhibition by Rhizobium can result in root hair curling when three conditions are simultaneously fulfilled: 1) rhizobial growth inhibition is strong enough to prevent removal out of the tip growth range: 2) root hair surface growth between the attached Rhizobium and the root hair top is inhibited; 3) rhizobial growth inhibition is limited to one side of the root hair.
The results predict that root hair curling by stimulation of tip growth is improbable. This study accentuates the need for information about the growth processes contributing to tip growth in leguminous root hairs.     

De novo formation and ultra-structural characterization of a fiber-producing human hair follicle equivalent in vitro

Across many tissues and organs, the ability to create an organoid, the smallest functional unit of an organ, in vitro is the key both to tissue engineering and preclinical testing regimes. The hair follicle is an organoid that has been much studied based on its ability to grow quickly and to regenerate after trauma. But hair follicle formation in vitro has been elusive. Replacing hair lost due to pattern baldness or more severe alopecia, including that induced by chemotherapy, remains a significant unmet medical need.By carefully analyzing and recapitulating the growth conditions of hair follicle formation, we recreated human hair follicles in tissue culture that were capable of producing hair. Our microfollicles contained all relevant cell types and their structure and orientation resembled in some ways excised hair follicle specimens from human skin. This finding offers a new window onto hair follicle development. Having a robust culture system for hair follicles is an important step towards improved hair regeneration as well as to an understanding of how marketed drugs or drug candidates, including cancer chemotherapy, will affect this important organ.     

The Patchwork Mouse Phenotype: Implication for Melanocyte Replacement in the Hair Follicle

Mice homozygous for the recessive patchwork (pwk) mutation are characterized by a variegated pigment pattern with a mixture of unpigmented and normally pigmented hairs. The pigmented hair bulbs contain functional melanocytes. By contrast, the unpigmented hair bulbs contain no melanocytes. This lack results from the death of melanoblasts in the hair follicle at the end of embryogenesis. Here, we report that melanoblasts and melanocytes are found in the epidermis of pwk/pwk mice. Furthermore, these epidermal pigment cells are able to colonize new hair follicles after skin wounding. Despite the presence of epidermal pigment cells with a colonization potential, a follicle that had produced an unpigmented hair produces a new unpigmented hair during the successive hair growth cycles. This hair color continuity is also true for the pigmented hair follicles. Thus, in normal conditions, the hair acts as an independent functional unit as regards its pigment cells population.     

Defective calmodulin-dependent rapid apical endocytosis in zebrafish sensory hair cell mutants.

Vertebrate mechanosensory hair cells contain a narrow "pericuticular" zone which is densely populated with small vesicles between the cuticular plate and cellular junctions near the apical surface. The presence of many cytoplasmic vesicles suggests that the apical surface of hair cells has a high turnover rate. The significance of intense membrane trafficking at the apical surface is not known. Using a marker of endocytosis, the styryl dye FM1-43, this report shows that rapid apical endocytosis in zebrafish lateral line sensory hair cells is calcium and calmodulin dependent and is partially blocked by the presence of amiloride and dihydrostreptomycin, known inhibitors of mechanotransduction channels. As seen in lateral line hair cells, sensory hair cells within the larval otic capsule also exhibit rapid apical endocytosis. Defects in internalization of the dye in both lateral line and inner ear hair cells were found in five zebrafish auditory/vestibular mutants: sputnik, mariner, orbiter, mercury, and skylab. In addition, lateral line hair cells in these mutants were not sensitive to prolonged exposure to streptomycin, which is toxic to hair cells. The presence of endocytic defects in the majority of zebrafish mechanosensory mutants points to a important role of apical endocytosis in hair cell function.     

Mesenchymal–epithelial interactions during hair follicle morphogenesis and cycling

Embryonic hair follicle induction and formation are regulated by mesenchymal–epithelial interactions between specialized dermal cells and epidermal stem cells that switch to a hair fate. Similarly, during postnatal hair growth, communication between mesenchymal dermal papilla cells and surrounding epithelial matrix cells coordinates hair shaft production. Adult hair follicle regeneration in the hair cycle again is thought to be controlled by activating signals originating from the mesenchymal compartment and acting on hair follicle stem cells. Although many signaling pathways are implicated in hair follicle formation and growth, the precise nature, timing, and intersection of these inductive and regulatory signals remains elusive. The goal of this review is to summarize our current understanding and to discuss recent new insights into mesenchymal–epithelial interactions during hair follicle morphogenesis and cycling.     

Extraction and Analysis of Cortisol from Human and Monkey Hair

The stress hormone cortisol (CORT) is slowly incorporated into the growing hair shaft of humans, nonhuman primates, and other mammals. We developed and validated a method for CORT extraction and analysis from rhesus monkey hair and subsequently adapted this method for use with human scalp hair. In contrast to CORT "point samples" obtained from plasma or saliva, hair CORT provides an integrated measure of hypothalamic-pituitary-adrenocortical (HPA) system activity, and thus physiological stress, during the period of hormone incorporation. Because human scalp hair grows at an average rate of 1 cm/month, CORT levels obtained from hair segments several cm in length can potentially serve as a biomarker of stress experienced over a number of months.In our method, each hair sample is first washed twice in isopropanol to remove any CORT from the outside of the hair shaft that has been deposited from sweat or sebum. After drying, the sample is ground to a fine powder to break up the hair''s protein matrix and increase the surface area for extraction. CORT from the interior of the hair shaft is extracted into methanol, the methanol is evaporated, and the extract is reconstituted in assay buffer. Extracted CORT, along with standards and quality controls, is then analyzed by means of a sensitive and specific commercially available enzyme immunoassay (EIA) kit. Readout from the EIA is converted to pg CORT per mg powdered hair weight. This method has been used in our laboratory to analyze hair CORT in humans, several species of macaque monkeys, marmosets, dogs, and polar bears. Many studies both from our lab and from other research groups have demonstrated the broad applicability of hair CORT for assessing chronic stress exposure in natural as well as laboratory settings.     

The age of hair matters – the incorporation of cortisol by external contamination is enhanced in distal hair segments of pigs and cattle

Hair cortisol concentration (HCC) is used as an indicator of long-term stress or pathologies in humans and increasingly in animals. Although the main mechanism for the incorporation of cortisol into the hair shaft is by diffusion from blood, cortisol may also be incorporated from external sources by contamination of the hair surface. In farm animals under conventional husbandry conditions and trapped animals, contamination of hair with cortisol-containing body fluids, especially with urine, was shown to be a considerable confounding factor when studying HCCs. We recently found that cattle and pigs exhibit elevated HCCs in distal hair segments and assume that the incorporation of external cortisol is facilitated in these older hair segments. Therefore, the aim of this study was to investigate the effects of urine contamination on HCC in different hair segments of pigs and cattle, and to determine whether different cleaning protocols can prevent contamination effects. In an in vivo experiment in pigs (n = 18) and an in vitro experiment in cattle (n = 12), hairs were repeatedly contaminated with urine of the respective species and then shaved or cut in segments. Cortisol concentrations in hair segments were analysed by enzyme immunoassay after washing with isopropanol and extraction with methanol. Results were compared with HCCs in untreated hairs or hairs treated with water. Moreover, additional bovine hair samples contaminated with urine were subjected to two further cleaning procedures. Contamination with urine generally increased HCCs, and it was demonstrated for the first time that this effect is more pronounced in distal compared to proximal hair segments in both species. The immersion of bovine hair in vitro in water caused a washout of cortisol, which was also more pronounced in distal hair segments. In general, the different cleaning protocols for cattle hair did not prevent contamination effects, so we assume that external cortisol not only adheres but is incorporated into the hair shaft. Structural damage of older, distal hair segments may facilitate permeability of the hair matrix and diffusion of cortisol from and into aqueous solutions. Thus, the validity of HCC as a marker of stress is compromised in animals where soiling of hair with body fluids is a risk factor. Therefore, hair samples should be collected from clean body regions and, if possible, using proximal hair segments.