Expression and transgenic studies of the mouse agouti gene provide insight into the mechanisms by which mammalian coat color patterns are generated

Development ◽  
1995 ◽  
Vol 121 (10) ◽  
pp. 3223-3232 ◽  
Author(s):  
S.E. Millar ◽  
M.W. Miller ◽  
M.E. Stevens ◽  
G.S. Barsh
Keyword(s):  
Coat Color ◽  
Dermal Papilla ◽  
Transgenic Animals ◽  
Branchial Arch ◽  
Hair Follicles ◽  
The Body ◽  
Basal Cells ◽  
Hair Cycle ◽  
Transplantation Experiments ◽  
Agouti Gene

Expression of the agouti gene from two different promoters, one active at the midpoint of the hair cycle and the other specific for the ventrum, is responsible for generating a range of mammalian pigmentation patterns. We demonstrate that in postnatal mice transcripts from both promoters are confined to the dermal papilla of hair follicles, as predicted by classical transplantation experiments. Transcripts from the hair cycle promoter are detected in the embryonic whisker plate but not in other regions of the body before birth, whereas ventral-specific transcripts are detected in the ventral trunk of the embryo as well as ventral whisker plate. To investigate further the embryonic origins of adult pigmentation patterns, we carried out a detailed analysis of agouti expression in the embryo. The ventral-specific agouti isoform is first expressed at E10.5 in neural crest-derived ventral cells of the second branchial arch, in anterior regions of the forelimb buds and in a narrow stripe of ventral mesenchyme. By E14.5 a continuous layer of expression is observed in the upper cells of the dermis, including cells of the developing dermal papillae, and covering the entire ventral surface of the head and trunk and dorsal surfaces of the distal forelimb and hindlimb. This expression pattern reflects the domain of yellow coloration evident in adult animals and suggests that the agouti gene is regulated in part by factors responsible for establishing differences between the dorsal and ventral surfaces of the body during embryogenesis. To test the hypothesis that agouti is a paracrine signaling molecule that can influence pigment production by hair follicle melanocytes when expressed by either dermis or epidermis, as suggested by recombination and transplantation experiments, we created transgenic animals in which agouti is expressed in basal cells of the epidermis. These animals display stripes of yellow hairs corresponding to regions of epidermal agouti expression, confirming that agouti signals melanocytes to synthesize yellow pigment and providing direct evidence that it functions in a paracrine manner with a restricted radius of action.

scholarly journals Inhibition of Rab27a and Rab27b Has Opposite Effects on the Regulation of Hair Cycle and Hair Growth

2020 ◽  
Vol 21 (16) ◽  
pp. 5672
Author(s):  
Kyung-Eun Ku ◽  
Nahyun Choi ◽  
Jong-Hyuk Sung
Keyword(s):  
Hair Growth ◽  
Expression Patterns ◽  
Dermal Papilla ◽  
Hair Follicles ◽  
Hair Cycle ◽  
Outer Root Sheath ◽  
Dermal Papilla Cells ◽  
Root Sheath ◽  
Culture Models

Rab27a/b are known to play an important role in the transport of melanosomes, with their knockout causing silvery gray hair. However, the relationship between Rab27a/b and hair growth is not well known. To evaluate the role of Rab27a/b in hair cycle, we investigated the expression of Rab27a/b during hair cycling and human outer root sheath (hORS) cells. The expression of Rab27a in ORS cells was mainly detected at the anagen, whereas expression of Rab27b in ORS, and epidermal cells was strongly expressed at the telogen. Additionally, Rab27a/b were expressed in the Golgi of hORS cells. To evaluate the role of Rab27a/b in hair growth, telogen-to-anagen transition animal and vibrissae hair follicles (HFs) organ culture models were assayed using Rab27a/b siRNAs. The knockdown of Rab27a or Rab27b suppressed or promoted hair growth, respectively. These results were also confirmed in human dermal papilla cells (hDPCs) and hORS cells, showing the opposite mitogenic effects. Moreover, Rab27b knockdown increased the expression levels of various growth factors in the hDPCs and hORS cells. Overall, the opposite temporal expression patterns during hair cycling and roles for hair growth of Rab27a/b suggested that Rab27a/b might regulate the hair cycle. Therefore, our study may provide a novel solution for the development of hair loss treatment by regulating Rab27a/b levels.

scholarly journals Dermal exosomes containing miR-218-5p promote hair regeneration by regulating β-catenin signaling

2020 ◽  
Vol 6 (30) ◽  
pp. eaba1685 ◽  
Author(s):  
Shiqi Hu ◽  
Zhenhua Li ◽  
Halle Lutz ◽  
Ke Huang ◽  
Teng Su ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Hair Growth ◽  
Dermal Papilla ◽  
Hair Follicles ◽  
Hair Cycle ◽  
Paracrine Signaling ◽  
Hair Regrowth ◽  
Study Results ◽  
Anagen Phase ◽  
Hair Follicle Cycle

The progression in the hair follicle cycle from the telogen to the anagen phase is the key to regulating hair regrowth. Dermal papilla (DP) cells support hair growth and regulate the hair cycle. However, they gradually lose key inductive properties upon culture. DP cells can partially restore their capacity to promote hair regrowth after being subjected to spheroid culture. In this study, results revealed that DP spheroids are effective at inducing the progression of the hair follicle cycle from telogen to anagen compared with just DP cell or minoxidil treatment. Because of the importance of paracrine signaling in this process, secretome and exosomes were isolated from DP cell culture, and their therapeutic efficacies were investigated. We demonstrated that miR-218-5p was notably up-regulated in DP spheroid–derived exosomes. Western blot and immunofluorescence imaging were used to demonstrate that DP spheroid–derived exosomes up-regulated β-catenin, promoting the development of hair follicles.

Morphological changes associated with the growth cycle of vibrissal follicles in the rat

Development ◽  
1976 ◽  
Vol 36 (3) ◽  
pp. 597-607
Author(s):  
R. D. Young ◽  
R. F. Oliver
Keyword(s):  
Morphological Changes ◽  
Dermal Papilla ◽  
Growth Cycle ◽  
Hair Follicles ◽  
Transitional Period ◽  
Hair Cycle ◽  
Hair Bulb ◽  
No Formation ◽  
The Matrix ◽  
Small Aggregation

Morphological changes which occur in the growth cycle of the rat vibrissal follicle during the transitional period between consecutive anagen phases are described. In contrast with pelage hair follicles, there is no shortening of the follicle, no formation of a papilla ‘rest’ and no close synchrony between club differentiation and follicle regression. Telogen is therefore considered to occur after loss of the matrix of the hair bulb and maximal diminution of the dermal papilla to a small aggregation of cells. These differences are discussed in relation to current nomenclature of the hair cycle and the function of the vibrissal follicle.

scholarly journals ‘Bare’, a new hairless mutant in the mouse—genetics and histology

1961 ◽  
Vol 2 (2) ◽  
pp. 283-289 ◽  
Author(s):  
Homai P. Randelia ◽  
L. D. Sanghvi
Keyword(s):  
Hair Follicles ◽  
Mouse Genetics ◽  
The Body ◽  
The Other ◽  
Hair Cycle ◽  
Hair Coat ◽  
Recessive Character ◽  
Sensory Hairs ◽  
Hereditary Defect ◽  
Air Cells

1. A new hereditary defect affecting the hair coat of Swiss albino mice is described. The defect was found to be inherited as a recessive character and is designated as bare (ba).2. The gene affected the vibrissae as well as pelage hairs. The lack of vibrissae and other sensory hairs at birth, helped to differentiate them easily from the normal animals. The first hairs on the body appeared at 13–14 days of age. The hairs were thin and tiny and remained there till about the thirtieth day. The hairs in the second hair cycle appeared at about 45 days, and again disappeared within 10 days. The animals were entirely naked when they were 6 months old.3. Gross as well as microscopic examination of hairs in the first hair cycle did not show the four different normal types of hairs. The hairs were comparatively very small, thin, and the internal structure did not show any regularity in the arrangement of the air cells.4. No difference was found in the number of hair follicles in the bare and the normal Swiss mice.5. Histology revealed the presence of keratinized globular masses instead of straight hair. This abnormality persisted in all the hair cycles.6. The bare mice were compared with the other mutants and placed in the Alopecia-Naked group where the abnormality was in the keratinization of the hair.

scholarly journals STRUCTURAL-FUNCTIONAL REORGANIZATION OF SKIN AND ITS DERIVATIVES UNDER EXPERIMENTAL SUBACUTE OF INTOXICATION BY HEAVY METALS

2019 ◽  
Vol 96 (6) ◽  
pp. 593-596
Author(s):  
Tatyana V. Nikolaeva ◽  
V. S. Polyakova ◽  
N. P. Setko ◽  
L. G. Voronina
Keyword(s):  
Heavy Metals ◽  
Proliferative Activity ◽  
Lead Acetate ◽  
Dermal Papilla ◽  
Hair Follicles ◽  
The Body ◽  
Acetate Solution ◽  
Sodium Dichromate ◽  
Ki 67 ◽  
Nickel Chromium

There was executed an experimental study of the effect of salts of heavy metals (nickel, chromium, lead and zinc) entering the body by peroral route, on the morphology of the skin and its derivatives (hair follicles and sebaceous glands). The experiment was performed on C57BL / 6 mice with the use of the induction of hair follicle cycle by depilation. Under the subacute intoxication with salts of nickel, chromium and lead, there were revealed such signs of a dystrophic anagen as ectopia of granules of melanin in the dermal papilla and perifollicular tissue, enlarged channels of the hair. The duration of the anagen stage if compared with the control did not change. Under the intoxication with salts of nickel and lead there was revealed infiltration by mononuclear dermis and hypodermis. Lead acetate gave rise in the capillary congestion of the dermis, followed by diapedesis of erythrocytes and infiltration of the dermis by siderophages. In the course of the immunohistochemical study of the proliferative activity of keratinocytes of the skin integument derivatives with the use of antibodies to Ki-67, there was revealed a significant increase of proliferative activity of keratinocytes in comparison with the control under the use of a solution of zinc sulphate and sodium dichromate and its decrease with the use of lead acetate solution.

The induction of hair follicle formation in the adult hooded rat by vibrissa dermal papillae

Development ◽  
1970 ◽  
Vol 23 (1) ◽  
pp. 219-236
Author(s):  
R. F. Oliver
Keyword(s):  
Hair Follicle ◽  
Hair Growth ◽  
Dermal Papilla ◽  
Hair Shaft ◽  
Hair Follicles ◽  
Hair Cycle ◽  
Hair Bulb ◽  
Essential Component ◽  
Dermal Papillae

Hair follicles are essentially composed of two tissues. The inner epidermal component, which gives rise to, among other products, the keratinized hair shaft, is confluent with the surface epidermis and is ensheathed by the dermal component which is confluent with the pars papillaris of the dermis. A specialization of the dermal component is the dermal papilla which, in follicles producing hair, is enclosed by the epidermal matrix of the hair bulb and is connected to the dermal sheath by the papilla stalk. Many authorities have considered that the dermal papilla is an essential component of the hair follicle (reviews: Cohen, 1965; Oliver, 1969). It has been suggested that the dermal papilla may be involved in both the induction of follicle lengthening and hair growth during the proanagen phase (Chase, 1965) of the hair cycle, a concept now justified by direct experimentation in the vibrissa follicle at least (Oliver, 1967b), and perhaps also in determining the nature of the hair produced by a follicle.

Cultured dermal papilla cells from androgen-dependent human hair follicles (e.g. beard) contain more androgen receptors than those from non-balding areas of scalp

1992 ◽  
Vol 133 (1) ◽  
pp. 141-147 ◽  
Author(s):  
V. A. Randall ◽  
M. J. Thornton ◽  
A. G. Messenger
Keyword(s):  
Hair Follicle ◽  
Human Hair ◽  
Androgen Receptors ◽  
Dermal Papilla ◽  
Hair Follicles ◽  
The Body ◽  
Follicular Epithelium ◽  
Dermal Papilla Cells ◽  
Age Related

ABSTRACT Androgens stimulate hair growth in many areas, e.g. the beard; they also induce regression and balding on the scalp with increasing age in genetically disposed individuals. The cause(s) of this biological conundrum is unknown but age-related; androgen-potentiated changes also occur in the prostate. The mesenchymederived dermal papilla situated at the base of the hair follicle is thought to play an important role in regulating the growth and development of the follicular epithelium. Since androgens probably act on the hair follicle via the dermal papilla, cultures of dermal papilla cells from human hair follicles with differing responses to androgens in vivo have been established and their ability to bind androgens assessed. Receptor binding was assayed by saturation analysis (0·05–10 nmol/l) using the synthetic non-metabolizable androgen, [3H]mibolerone. Shionogi 115 cells were also assayed as a positive control. Specific high-affinity low-capacity androgen receptors were identified in 12 dermal papilla primary cell lines with similar characteristics to established androgen receptors. Cells from androgen-sensitive follicles (beard, scrotum and pubis) contained higher levels of androgen receptors than those derived from relatively androgeninsensitive non-balding scalp follicles whether the receptor content was calculated in relation to cell number, protein or DNA content of the cells. These results support the hypothesis that androgens act on hair follicles via the dermal papilla in vivo and demonstrate that dermal papilla cells exhibit an altered phenotype in culture which depends on the body site from which they were derived. Cultured human dermal papilla cells should prove a useful model system for studies of the mechanism of androgen action, and further investigations may elucidate the paradox of why bald men can grow beards. Journal of Endocrinology (1992) 133, 141–147

scholarly journals Hormonal Effects on Hair Follicles

2020 ◽  
Vol 21 (15) ◽  
pp. 5342 ◽  
Author(s):  
Monika Grymowicz ◽  
Ewa Rudnicka ◽  
Agnieszka Podfigurna ◽  
Paulina Napierala ◽  
Roman Smolarczyk ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Hair Growth ◽  
Dermal Papilla ◽  
Dehydroepiandrosterone Sulfate ◽  
Hair Follicles ◽  
The Body ◽  
Aromatase Activity ◽  
Hormonal Changes ◽  
Dermal Papilla Cells ◽  
Intracellular Enzyme

The hair cycle and hair follicle structure are highly affected by various hormones. Androgens—such as testosterone (T); dihydrotestosterone (DHT); and their prohormones, dehydroepiandrosterone sulfate (DHEAS) and androstendione (A)—are the key factors in terminal hair growth. They act on sex-specific areas of the body, converting small, straight, fair vellus hairs into larger darker terminal hairs. They bind to intracellular androgen receptors in the dermal papilla cells of the hair follicle. The majority of hair follicles also require the intracellular enzyme 5-alpha reductase to convert testosterone into DHT. Apart from androgens, the role of other hormones is also currently being researched—e.g., estradiol can significantly alter the hair follicle growth and cycle by binding to estrogen receptors and influencing aromatase activity, which is responsible for converting androgen into estrogen (E2). Progesterone, at the level of the hair follicle, decreases the conversion of testosterone into DHT. The influence of prolactin (PRL) on hair growth has also been intensively investigated, and PRL and PRL receptors were detected in human scalp skin. Our review includes results from many analyses and provides a comprehensive up-to-date understanding of the subject of the effects of hormonal changes on the hair follicle.

scholarly journals Localization of TIMP in cycling mouse hair

Development ◽  
1991 ◽  
Vol 111 (4) ◽  
pp. 877-879
Author(s):  
T.T. Kawabe ◽  
T.J. Rea ◽  
A.M. Flenniken ◽  
B.R. Williams ◽  
V.E. Groppi ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Gene Activation ◽  
Dermal Papilla ◽  
Growth Cycle ◽  
Hair Follicles ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Hair Cycle ◽  
Dermal Papilla Cells ◽  
Root Sheath ◽  
Timp Gene

TIMP (tissue inhibitor of metalloproteinase) is a glycoprotein inhibitor of metalloproteinases that we hypothesize to be involved in the tissue remodeling that occurs during each hair growth cycle. We examined this hypothesis by studying the expression of TIMP at selected times during a single hair cycle using TIMP-lacZ transgenic mice to localize TIMP gene activity in the hair follicle. TIMP gene induction was visualized by staining mouse back skin for beta-galactosidase (beta-gal) activity. Paraffin sections were analyzed for the localization of TIMP expression. TIMP gene activation appears in hair follicles only during the mid-anagen (the growing stage of the hair cycle) primarily in Henle's layer of the inner root sheath. Some expression of TIMP is also seen in a few connective tissue cells, in the sebaceous gland and in cells at the proximity of the dermal papilla cells in catagen (regressing) and telogen (resting) follicles. These results are consistent with a role for TIMP in cyclic remodeling of connective tissue in hair follicles.

Formulation, Design and Development of Niosome Based Topical Gel for Skin Cancer

2017 ◽  
Vol 2 (3) ◽  
Keyword(s):  
Skin Cancer ◽  
Drug Release ◽  
Hemorrhagic Cystitis ◽  
The Body ◽  
Cancer Drug ◽  
Inversion Method ◽  
Body Parts ◽  
Basal Cells ◽  
Formulation Design ◽  
Topical Gel

Melanoma is the most dangerous type of skin cancer in which mostly damaged unpaired DNA starts mutating abnormally and staged an unprecedented proliferation of epithelial skin to form a malignant tumor. In epidemics of skin, pigment-forming melanocytes of basal cells start depleting and form uneven black or brown moles. Melanoma can further spread all over the body parts and could become hard to detect. In USA Melanoma kills an estimated 10,130 people annually. This challenge can be succumbed by using the certain anti-cancer drug. In this study design, cyclophosphamide were used as a model drug. But it has own limitation like mild to moderate use may cause severe cytopenia, hemorrhagic cystitis, neutropenia, alopecia and GI disturbance. This is a promising challenge, which is caused due to the increasing in plasma drug concentration above therapeutic level and due to no rate limiting steps involved in formulation design. In this study, we tried to modify drug release up to threefold and extended the release of drug by preparing and designing niosome based topical gel. In the presence of Dichloromethane, Span60 and cholesterol, the initial niosomes were prepared using vacuum evaporator. The optimum percentage drug entrapment efficacy, zeta potential, particle size was found to be 72.16%, 6.19mV, 1.67µm.Prepared niosomes were further characterized using TEM analyzer. The optimum batch of niosomes was selected and incorporated into topical gel preparation. Cold inversion method and Poloxamer -188 and HPMC as core polymers, were used to prepare cyclophosphamide niosome based topical gel. The formula was designed using Design expert 7.0.0 software and Box-Behnken Design model was selected. Almost all the evaluation parameters were studied and reported. The MTT shows good % cell growth inhibition by prepared niosome based gel against of A375 cell line. The drug release was extended up to 20th hours. Further as per ICH Q1A (R2), guideline 6 month stability studies were performed. The results were satisfactory and indicating a good formulation approach design was achieved for Melanoma treatment.

Sign in / Sign up

Export Citation Format

Share Document