Secondary Hair Research Articles

Expression and localization of the vascular endothelial growth factor and changes of microvessel density during hair follicle development of Liaoning cashmere goats

Vascular endothelial growth factors (VEGFs) play important roles in neovascularization, tissue development, and angiogenesis. In this study, changes in VEGF expression patterns and microvessel density (MVD), and their correlations, were investigated during hair follicle development in epidermal appendages of Liaoning cashmere goats. Polyclonal antibodies to VEGF and microvessels were used for monthly immunohistochemical examinations of normal skin specimens from adult female goats for one year. VEGF was expressed in the hair bulb of primary and secondary hair follicles, the outer and inner root sheaths, sebaceous glands (ductal and secretory portions), eccrine sweat glands (ductal and secretory portions), and the epidermis. Abundant expression of VEGF was observed in the follicular basement membrane zone surrounding the bulb matrix and in ductal and secretory portions of eccrine sweat glands. The change in VEGFs in primary hair follicles showed a bimodal pattern, with the first peak observed from March to May, and the second in August. Maximal expression in secondary hair follicles occurred in May and August. Therefore, VEGF expression in primary and secondary hair follicles is synchronized throughout the year, and is correlated to hair development. In the later telogen and anagen phases, VEGF expression was higher in the secondary, compared to the primary, hair follicle. Changes in MVD also showed a bimodal pattern with peaks in May and August. VEGF expression and MVD showed moderate and strongly positive correlation in the primary and secondary hair follicles, respectively. Therefore, MVD and VEGF are closely related to the processes involved in hair cycle regulation.

A Spontaneous Fatp4/Scl27a4 Splice Site Mutation in a New Murine Model for Congenital Ichthyosis

Congenital ichthyoses are life-threatening conditions in humans. We describe here the identification and molecular characterization of a novel recessive mutation in mice that results in newborn lethality with severe congenital lamellar ichthyosis. Mutant newborns have a taut, shiny, non-expandable epidermis that resembles cornified manifestations of autosomal-recessive congenital ichthyosis in humans. The skin is stretched so tightly that the newborn mice are immobilized. The genetic defect was mapped to a region near the proximal end of chromosome 2 by SNP analysis, suggesting Fatp4/Slc27a4 as a candidate gene. FATP4 mutations in humans cause ichthyosis prematurity syndrome (IPS), and mutations of Fatp4 in mice have previously been found to cause a phenotype that resembles human congenital ichthyoses. Characterization of the Fatp4 cDNA revealed a fusion of exon 8 to exon 10, with deletion of exon 9. Genomic sequencing identified an A to T mutation in the splice donor sequence at the 3′-end of exon 9. Loss of exon 9 results in a frame shift mutation upstream from the conserved very long-chain acyl-CoA synthase (VLACS) domain. Histological studies revealed that the mutant mice have defects in keratinocyte differentiation, along with hyperproliferation of the stratum basale of the epidermis, a hyperkeratotic stratum corneum, and reduced numbers of secondary hair follicles. Since Fatp4 protein is present primarily at the stratum granulosum and the stratum spinosum, the hyperproliferation and the alterations in hair follicle induction suggest that very long chain fatty acids, in addition to being required for normal cornification, may influence signals from the stratum corneum to the basal cells that help to orchestrate normal skin differentiation.

Differential response of epithelial stem cell populations in hair follicles to TGF-β signaling

Epidermal stem cells residing in different locations in the skin continuously self-renew and differentiate into distinct cell lineages to maintain skin homeostasis during postnatal life. Murine epidermal stem cells located at the bulge region are responsible for replenishing the hair lineage, while the stem cells at the isthmus regenerate interfollicular epidermis and sebaceous glands. In vitro cell culture and in vivo animal studies have implicated TGF-β signaling in the maintenance of epidermal and hair cycle homeostasis. Here, we employed a triple transgenic animal model that utilizes a combined Cre/loxP and rtTA/TRE system to allow inducible and reversible inhibition of TGF-β signaling in hair follicle lineages and suprabasal layer of the epidermis. Using this animal model, we have analyzed the role of TGF-β signaling in distinct phases of the hair cycle. Transient abrogation of TGF-β signaling does not prevent catagen progression; however, it induces aberrant proliferation and differentiation of isthmus stem cells to epidermis and sebocyte lineages and a blockade in anagen re-entry as well as results in an incomplete hair shaft development. Moreover, ablation of TGF-β signaling during anagen leads to increased apoptosis in the secondary hair germ and bulb matrix cells. Blocking of TGF-β signaling in bulge stem cell cultures abolishes their colony-forming ability, suggesting that TGF-β signaling is required for the maintenance of bulge stem cells. At the molecular level, inhibition of TGF-β signaling results in a decrease in both Lrig1-expressing isthmus stem cells and Lrg5-expressing bulge stem cells, which may account for the phenotypes seen in our animal model. These data strongly suggest that TGF-β signaling plays an important role in regulating the proliferation, differentiation, and apoptosis of distinct epithelial stem cell populations in hair follicles.

Mutant laboratory mice with abnormalities in hair follicle morphogenesis, cycling, and/or structure: An update

Human hair disorders comprise a number of different types of alopecia, atrichia, hypotrichosis, distinct hair shaft disorders as well as hirsutism and hypertrichosis. Their causes vary from genodermatoses (e.g. hypotrichoses) via immunological disorders (e.g. alopecia areata, autoimmune cicatrical alopecias) to hormone-dependent abnormalities (e.g. androgenetic alopecia). A large number of spontaneous mouse mutants and genetically engineered mice develop abnormalities in hair follicle morphogenesis, cycling, and/or hair shaft formation, whose analysis has proven invaluable to define the molecular regulation of hair growth, ranging from hair follicle development, and cycling to hair shaft formation and stem cell biology. Also, the accumulating reports on hair phenotypes of mouse strains provide important pointers to better understand the molecular mechanisms underlying human hair growth disorders. Since numerous new mouse mutants with a hair phenotype have been reported since the publication of our earlier review on this matter a decade ago, we present here an updated, tabulated mini-review. The updated annotated tables list a wide selection of mouse mutants with hair growth abnormalities, classified into four categories: Mutations that affect hair follicle (1) morphogenesis, (2) cycling, (3) structure, and (4) mutations that induce extrafollicular events (for example immune system defects) resulting in secondary hair growth abnormalities. This synthesis is intended to provide a useful source of reference when studying the molecular controls of hair follicle growth and differentiation, and whenever the hair phenotypes of a newly generated mouse mutant need to be compared with existing ones.

Conformally coupled scalar black holes admit a flat horizon due to axionic charge

Abstract Static, charged black holes in the presence of a negative cosmological constant and with a planar horizon are found in four dimensions. The solutions have scalar secondary hair. We claim that these constitute the planar version of the Martínez-Troncoso-Zanelli black holes, only known up to now for a curved event horizon in four dimensions. Their planar version is rendered possible due to the presence of two, equal and homogeneously distributed, axionic charges dressing the flat horizon. The solutions are presented in the conformal and minimal frame and their basic properties and thermodynamics analysed. Entertaining recent applications to holographic superconductors, we expose two branches of solutions: the undressed axionic Reissner-Nordström-AdS black hole, and the novel black hole carrying secondary hair. We show that there is a critical temperature at which the (bald) axionic Reissner-Nordström-AdS black hole undergoes a second order phase transition to the hairy black hole spontaneously acquiring scalar hair.

Effect of age and sex on fiber and follicle characteristics of an Iranian native sheep

The mammalian hair fibers represent an interesting biological material which also is used in the textile industry. Histological structures of the fibers and follicles differ not only among different species but also among different areas and ages in an animal species. Skin samples were collected from neonatal (1-2 months), young (3-9 months), young adult (1-2 years) and old adult age groups (3 years and more). In each age group, six animals (3 each sex) were utilized. Immediately after slaughtering the animals, tissues were collected from eight regions namely belly, neck, leg, rump, flank, forearm, shoulder and hip and were fixed in 10 percent neutral buffered formalin. Histologic sections were stained with hematoxylin-eosin and special stains. It was found that the general histological features of all Bakhtiari sheep fibers used in this study were similar to many other breeds sited in literature, however there were also some differences. All hairs of the various skin regions had a medulla. All the hair follicles were surrounded by associated structures such as the sweat and sebaceous glands and arrector pili muscles and located only in papillary layer of the dermis. The most common number of the secondary hair follicles in compound hair follicles was 4. The histology of all fibers and follicles in various skin regions showed no significant differences by sex in all the age groups studied. By age increase, all the fibers and their follicles were larger and well organized in all different skin regions.

Comparison of two shampoos as sole treatment for canine bacterial overgrowth syndrome

Two antibacterial shampoos for the treatment of canine bacterial overgrowth syndrome (BOGS) were compared in a prospective controlled clinical trial. Forty dogs with clinical signs (pruritus, erythema and excoriations without...

Black holes with primary hair in gauged N = 8 supergravity

In this paper, we analyze the static solutions for the $U(1)^{4}$ consistent truncation of the maximally supersymmetric gauged supergravity in four dimensions. Using a new parametrization of the known solutions it is shown that for fixed charges there exist three possible black hole configurations according to the pattern of symmetry breaking of the (scalars sector of the) Lagrangian. Namely a black hole without scalar fields, a black hole with a primary hair and a black hole with a secondary hair respectively. This is the first, exact, example of a black hole with a primary scalar hair, where both the black hole and the scalar fields are regular on and outside the horizon. The configurations with secondary and primary hair can be interpreted as a spontaneous symmetry breaking of discrete permutation and reflection symmetries of the action. It is shown that there exist a triple point in the thermodynamic phase space where the three solution coexist. The corresponding phase transitions are discussed and the free energies are written explicitly as function of the thermodynamic coordinates in the uncharged case. In the charged case the free energies of the primary hair and the hairless black hole are also given as functions of the thermodynamic coordinates.

Premature adrenarche: an audit of endocrine profile and management in the outpatient setting

Aims Premature adrenarche (PA) is a common reason for referral to a paediatric clinic. There is little data on the clinical characteristics of these patients from the United Kingdom. Our aim is to audit the clinical presentation and management of PA in the outpatient setting. Subjects and methods The auxology, pubertal status and endocrine profile of all children with a diagnosis of PA in an inner-city hospital from 1/1/2010 to 31/12/2010 were retrospectively audited. Results A total of 37 children were identified, the majority of whom were girls (84%). The mean age at presentation was 7.06 years (±2.26 years). 20/37 (54%) children were of an ethnic minority background, and the mean duration of symptoms was relatively long at 14.2 months. The mean height and weight SDS were 1.09 (±1.38) and 0.86 (±1.2) respectively. Although boys tended to be smaller, the mean BMI SDS was comparable (boys 0.83; girls 0.93). The majority of children presented with axillary hair stage 1 (84%) and pubic hair stage 2 (54%). Body odour was also a complaint in 54% of cases. Whilst all male patients were pre-pubertal, 26% of the older girls (mean age 9.13 years) had evidence of breast development. Most (89%) children had their 17 hydroxyprogesterone (mean 4.08±2.2 nmol/L) measured. Other adrenal androgens and testosterone levels were normal in all patients who were tested. Only a minority had gonadotrophins (40%) and bone age (46%) estimated. We proceeded to a Synacthen test in only three children (basal 17 hydroxyprogesterone levels of 2.3, 7.8 and 12.3 nmol/L). No underlying pathology was identified in any of these children, and the average length of follow-up was 5 months. Conclusion Our audit demonstrates that parental concern over secondary sexual hair growth is a relatively common presentation in paediatric clinics. It is more common in girls presenting in a pre-pubertal state, with a small subset of older girls who may be pubertal with an antecedent history of PA. Baseline endocrine profile is reassuring in the vast majority and further dynamic testing is rarely needed. Our audit identified no underlying disease in this patient group.

Abstract 4178: Tcl1 enhances keratinocytes’ survival/proliferation by promoting erk and jnk/sap phosphorylation at the expense of p38 and by controlling c-fos expression through miR-29b and miR-181a-1

Abstract The Tcl1 oncogene has been initially isolated for its involvement in chromosomal translocations of T-prolymphocytic leukemias and overexpression in B chronic lymphocytic leukemia by enhancing AKT nuclear translocation and allowing the Ser-473 transphosphorylation. Tcl1, also, acts as AP-1 transcriptional inhibitor, by interacting with c-fos and c-jun. More recent works have associated Tcl1 to proliferation and self-renewal ability of ES cells under the direct activation of OCT3/4, Zfx, KLF5 transcription factors, being Tcl1 expressed in preimplantation embryos where it allows the progression beyond the 4-cells stage. We have recently shown that the Tcl1 oncogene is expressed in epidermis and defines secondary hair germ (transient-amplifying, TA) cells differentiation at catagen-telogen (the degenerative-resting phase of the hair follicle (HF)) transition, allowing the proliferation of TA cells in anagen (regenerative phase of the HF), giving the slow-cycling stem cells, the ability to incorporate BrdU. In fact, Tcl1 mutant (Tcl1-/-) affects stem-cell marker CD34 expression and BrdU incorporation in the bulge and TA cells, resulting in skin defects in adults with the onset of alopecia followed by skin wounding. Phenomena that are almost completely rescued by K14-TCL1 transgenic expression, in vivo. Since Tcl1 has a role in maintenance of a normal skin homeostasis in mice, involving both hair growth and epidermis, we used the approach of the expression chip analysis to unravel the pathways that are affected by loss of function and overexpression of Tcl1 in epidermal keratinocytes, by using Tcl1-/- and K14-TCL1;Tcl1-/- mice models. Our findings show that Tcl1 function involves the MAPK pathway, since Tcl1-/- shows increasing in p38MAPK phosphorylation linked to terminal differentiation/senescence/apoptosis of keratinocytes, while K14-driven overexpression shows increasing of p-Erk and p-Sapk/p-Jnk phosphorylations, linked to proliferation/commitment of keratinocytes. These signals flow through the MAPK cascade lead to altered AP1 factor function. In particular, the phosphorylation of AP-1 subunit c-Jun and c-fos transcriptional regulation and cellular localization result also affected. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4178. doi:1538-7445.AM2012-4178

Abstract SY37-01: Cilia and wounding cooperate with Hedgehog signaling to initiate basal cell carcinoma

Abstract Primary cilia are microtubule-based projections found on many human cells. These cilia do not move, but function as cellular antennae to receive and interpret signals. For example, olfactory cilia sense odorants in the environment. Other cilia sense cues from other cells, such as Hedgehog proteins, to coordinate tissue patterning and growth. We have identified mechanisms of ciliary signaling, cilium formation, and the regulation of ciliary composition. Defects in ciliary signaling cause some forms of birth defects, cancer, polycystic kidney disease, and other disorders collectively called ciliopathies. To examine whether cilia can participate in disorders beyond recognized ciliopathies, we assessed the prevalence of cilia in human tumors and the role of cilia in cancer. Human basal cell carcinomas (BCCs) are associated with misactivation of Hedgehog signaling, commonly through acquisition of mutations in Smoothened. We found that human BCCs are frequently ciliated. We tested the role of cilia in BCC by conditionally deleting genes required for ciliogenesis in a Hedgehog pathway-dependent mouse model of BCC. Ciliary ablation strongly inhibited BCC-like tumors induced by misactivation of the Hedgehog pathway at the level of Smoothened, revealing that BCC can be addicted to cilia. Skin tumors, like many other cancers, are associated with injury. Although stem cells participate in tissue regeneration after wounding, it is unclear whether these cells also contribute to epithelial tumors. Surprisingly, expression of an activated form of Smoothened by stem cells of the hair-follicle bulge and secondary hair germ does not induce robust Hedgehog signaling or produce BCCs. However, wounding recruits these cells from the follicle to the wound site, where downstream Hedgehog signal transduction is derepressed, giving rise to superficial BCC-like tumors. Thus, BCCs can originate from follicular stem cells and wounding can promote tumorigenesis by moving oncogene-expressing stem cells out of a suppressive niche. As we found that oncogenic Smoothened requires the cilium to promote tumorigenesis, we investigated how Smoothened moves to the cilium. We found that proteins of the Tectonic family form part of the transition zone, a region at the base of the cilium. Tectonic1 is an extracytosolic glycoprotein that interacts with transmembrane components of the transition zone to connect to a cytosolic transition zone complex comprised of the products of genes associated with two ciliopathies, Joubert and Meckel syndromes. Loss of components of the Tectonic transition zone complex in mice compromise ciliogenesis in some tissues, but in others, it is required for Smoothened and select other membrane proteins to localize to cilia. A complementary small molecule screen is identifying new chemicals that also prevent Smoothened localization to cilia and block oncogenic Hedgehog signaling. Interfering with the cellular machinery that moves Smoothened to cilia may be a complementary means of treating Hedgehog pathway-associated cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY37-01. doi:1538-7445.AM2012-SY37-01

Identification of Genes Preferentially Expressed in Goat Hair Follicle Anagen-Catagen Transition Using Suppression Subtractive Hybridization

Suppressive subtraction hybridization (SSH) was used to identify differentially expressed genes in goat (Capra hircus) hair follicle anagen-catagen transition. The cDNA fragments, derived from SSH positive subtractive library (tester: anagen-catagen transition, driver: later anagen), were cloned into pEGM-T vector. Two hundred cDNA fragments screened from this library were subjected to identify forty-five unregulated isolates. Sequence analysis revealed that these fragments represented twenty-three genes. Blasting analysis with database in GenBank showed that twenty genes were previously clearly annotated, two were homologous to un-annotated expressed sequence tag (ESTs), and one might be novel. To identify characters of gene expression, seven genes in later anagen and anagen-catagen transition skin tissues were chosen for quantitative real-time PCR. Results indicated that expression of these seven genes varied much, reaching threefold among them, furthering indicating that expression of those genes was up-regulation in the anagen-catagen transition. We characterized expression levels of this potential novel gene and the goat ectodysplasin A during differential stages of hair cycle. These profiles suggested that these two genes might play a role in the goat secondary hair follicle cycle.

The 5 Alpha-Reductase Isozyme Family: A Review of Basic Biology and Their Role in Human Diseases

Despite the discovery of 5 alpha-reduction as an enzymatic step in steroid metabolism in 1951, and the discovery that dihydrotestosterone is more potent than testosterone in 1968, the significance of 5 alpha-reduced steroids in human diseases was not appreciated until the discovery of 5 alpha-reductase type 2 deficiency in 1974. Affected males are born with ambiguous external genitalia, despite normal internal genitalia. The prostate is hypoplastic, nonpalpable on rectal examination and approximately 1/10th the size of age-matched normal glands. Benign prostate hyperplasia or prostate cancer does not develop in these patients. At puberty, the external genitalia virilize partially, however, secondary sexual hair remains sparse and male pattern baldness and acne develop rarely. Several compounds have been developed to inhibit the 5 alpha-reductase isozymes and they play an important role in the prevention and treatment of many common diseases. This review describes the basic biochemical properties, functions, tissue distribution, chromosomal location, and clinical significance of the 5 alpha-reductase isozyme family.

Hair loss in women: medical and cosmetic approaches to increase scalp hair fullness

Androgenetic alopecia affects both men and women. In men it produces male pattern hair loss with bitemporal recession and vertex baldness. In women it produces female pattern hair loss (FPHL) with diffuse alopecia over the mid-frontal scalp. FPHL occurs as a result of nonuniform hair follicle miniaturization within follicular units. Diffuse alopecia is produced by a reduction in the number of terminal fibres per follicular unit. Baldness occurs only when all hairs within the follicular units are miniaturized and is a relatively late event in women. The concepts of follicular units and primary and secondary hair follicles within follicular units are well established in comparative mammalian studies, particularly in sheep. However, discovery of these structures in the human scalp hair and investigation of the changes in follicular unit anatomy during the development of androgenetic alopecia have provided a clearer understanding of the early stages of androgenetic alopecia and how the male and female patterns of hair loss are related. FPHL is the most common cause of alopecia in women and approximately one-third of adult caucasian women experience hair loss. The impact of FPHL is predominantly psychological. While men anticipate age-related hair loss, hair loss in women is usually unexpected and unwelcome at any age. Treatment options to arrest hair loss progression and stimulate partial hair regrowth for FPHL include the androgen receptor antagonists spironolactone and cyproterone acetate, the 5α-reductase inhibitor finasteride and the androgen-independent hair growth stimulator minoxidil. These treatments appear to work best when initiated early. Hair transplantation should be considered in advanced FPHL that is resistant to medical treatments. Hair transplantation requires well-preserved hair growth over the occipital donor area. The psychological impact of FPHL may also be reduced by cosmetic products that improve the appearance of the hair. These agents work to minimize hair fibre breakage, improve hair volume or conceal visible bald scalp.

Lhx2 differentially regulates Sox9, Tcf4 and Lgr5 in hair follicle stem cells to promote epidermal regeneration after injury

The Lhx2 transcription factor plays essential roles in morphogenesis and patterning of ectodermal derivatives as well as in controlling stem cell activity. Here, we show that during murine skin morphogenesis, Lhx2 is expressed in the hair follicle (HF) buds, whereas in postnatal telogen HFs Lhx2(+) cells reside in the stem cell-enriched epithelial compartments (bulge, secondary hair germ) and co-express selected stem cell markers (Sox9, Tcf4 and Lgr5). Remarkably, Lhx2(+) cells represent the vast majority of cells in the bulge and secondary hair germ that proliferate in response to skin injury. This is functionally important, as wound re-epithelization is significantly retarded in heterozygous Lhx2 knockout (+/-) mice, whereas anagen onset in the HFs located closely to the wound is accelerated compared with wild-type mice. Cell proliferation in the bulge and the number of Sox9(+) and Tcf4(+) cells in the HFs closely adjacent to the wound in Lhx2(+/-) mice are decreased in comparison with wild-type controls, whereas expression of Lgr5 and cell proliferation in the secondary hair germ are increased. Furthermore, acceleration of wound-induced anagen development in Lhx2(+/-) mice is inhibited by administration of Lgr5 siRNA. Finally, Chip-on-chip/ChIP-qPCR and reporter assay analyses identified Sox9, Tcf4 and Lgr5 as direct Lhx2 targets in keratinocytes. These data strongly suggest that Lhx2 positively regulates Sox9 and Tcf4 in the bulge cells, and promotes wound re-epithelization, whereas it simultaneously negatively regulates Lgr5 in the secondary hair germ and inhibits HF cycling. Thus, Lhx2 operates as an important regulator of epithelial stem cell activity in the skin response to injury.

Shh is required for Tabby hair follicle development

In embryonic Eda mutant ("Tabby") mice, the development of one of the two major types of hair, "primary" hair fails, but other "secondary" hairs develop in normal numbers, though shorter and slightly aberrant. In Tabby mice, Shh is undetectable in skin early on, but is activated during secondary hair formation. We inferred that Shh may be involved in primary hair formation, activated normally by Eda, and also possibly in secondary hair formation, activated by an Eda-independent pathway. Varying the dosage of Shh now supports these inferences. In Shh knockout mice, mice were totally hairless: primary and secondary hair follicle germs were formed, but further progression failed. Consistent with these findings, when Shh loss was restricted to the skin, secondary hair follicle germs were initiated on time in Tabby mice, but their subsequent development (down-growth) failed. An Shh transgene expressed in Tabby skin could not restore induction of primary hair follicles, but restored normal length to the somewhat aberrant secondary hair that was formed and prolonged the anagen phase of hair cycling. Thus, Shh is required for primary and secondary hair down-growth and full secondary hair length, but is not itself sufficient to replace Eda or make fully normal secondary hair.

Improved fetal hair follicle development by maternal supplement of selenium at nano size (Nano-Se)

To investigate the effect of maternal and dietary selenium on antioxidant status and hair follicle development in 110-day fetal skin from cashmere goats, eighty selected cashmere goats (n=80) were randomly divided in two groups, C group (fed with the basal diet) and S group (fed with the basal diet with 0.5mg/kg Nano-Se). Nano-Se was supplemented from 30days prior to gestation to fetal day 110. Samples of fetus on day 110 have shown that the expression of GSH-Px, IGF-1 and IGF-1R, as well as the activities of GSH-Px and SOD, were significantly higher in S group than those in C group. The MDA level was significantly lower in S group. The concentrations of IGF-1, Se and T-AOC in both fetal serum and skin were significantly increased in S group. Weights of fetal liver and kidney tissues were also significantly increased in S group. Histology assay indicated that there was no significant difference in the number of primary hair follicles between the two groups. However, the number of secondary hair follicles and the secondary to primary follicle (S/P) ratio was significantly higher in S group than those in C group, indicating that the Nano-Se supplement could promote the development of secondary follicles. Our results demonstrate that maternal supplement of Nano-Se could influence antioxidant status in the fetal skin, the resulted low ROS could up-regulate IGF-1 and IGF-1R, which improve the fetal hair follicle development and promote the growth development of fetal. Results of present study suggest that maternal dietary supplements of Nano-Se during gestation could be used to improve the hair follicle development and promote growth development in Cashmere goat fetus.

Coordinated Activation of Wnt in Epithelial and Melanocyte Stem Cells Initiates Pigmented Hair Regeneration

Melanocyte stem cells (McSCs) intimately interact with epithelial stem cells (EpSCs) in the hair follicle bulge and secondary hair germ (sHG). Together, they undergo activation and differentiation to regenerate pigmented hair. However, the mechanisms behind this coordinated stem cell behavior have not been elucidated. Here, we identified Wnt signaling as a key pathway that couples the behavior of the two stem cells. EpSCs and McSCs coordinately activate Wnt signaling at the onset of hair follicle regeneration within the sHG. Using genetic mouse models that specifically target either EpSCs or McSCs, we show that Wnt activation in McSCs drives their differentiation into pigment-producing melanocytes, while EpSC Wnt signaling not only dictates hair follicle formation but also regulates McSC proliferation during hair regeneration. Our data define a role for Wnt signaling in the regulation of McSCs and also illustrate a mechanism for regeneration of complex organs through collaboration between heterotypic stem cell populations.

Basal cell carcinomas in mice arise from hair follicle stem cells and multiple epithelial progenitor populations

Uncontrolled Hedgehog (Hh) signaling leads to the development of basal cell carcinoma (BCC), the most common human cancer, but the cell of origin for BCC is unclear. While Hh pathway dysregulation is common to essentially all BCCs, there exist multiple histological subtypes, including superficial and nodular variants, raising the possibility that morphologically distinct BCCs may arise from different cellular compartments in skin. Here we have shown that induction of a major mediator of Hh signaling, GLI2 activator (GLI2ΔN), selectively in stem cells of resting hair follicles in mice, induced nodular BCC development from a small subset of cells in the lower bulge and secondary hair germ compartments. Tumorigenesis was markedly accelerated when GLI2ΔN was induced in growing hair follicles. In contrast, induction of GLI2ΔN in epidermis led to the formation of superficial BCCs. Expression of GLI2ΔN at reduced levels in mice yielded lesions resembling basaloid follicular hamartomas, which have previously been linked to low-level Hh signaling in both mice and humans. Our data show that the cell of origin, tissue context (quiescent versus growing hair follicles), and level of oncogenic signaling can determine the phenotype of Hh/Gli-driven skin tumors, with high-level signaling required for development of superficial BCC-like tumors from interfollicular epidermis and nodular BCC-like tumors from hair follicle stem cells.

Identification of cannabinoid type 1 receptor in dog hair follicles

In veterinary medicine, there is an increasing interest in the study of the endo-cannabinoid system and the possible use of the cannabinoids for the treatment of several diseases. Cannabinoid receptors (CB) are widely distributed in human and laboratory animal tissues, justifying the involvement of the endo-cannabinoid system in a great number of metabolic ways. Since there are no data regarding cannabinoid receptors in hair follicles of domestic animals, we investigated the presence and localization of CB1 receptor in dog hair follicles. By using a goat anti-CB1 polyclonal antibody, we observed CB1 receptor in the proximal part of both primary and secondary hair follicles. Staining was localized in the inner root sheath cells. We suppose that the endo-cannabinoid system is involved in the molecular mechanisms regulating hair follicle activity in dog. The identification of CB1 receptor at the level of the inner root sheath may help in the understanding of hair follicle biology and the possibility that cannabinoid molecules could be considered as suitable therapeutic tools in dog.