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

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.

2020 ◽  
Vol 6 (30) ◽  
pp. eaba1685 ◽  
Author(s):  
Shiqi Hu ◽  
Zhenhua Li ◽  
Halle Lutz ◽  
Ke Huang ◽  
Teng Su ◽  
...  

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.


2016 ◽  
Vol 473 (19) ◽  
pp. 3291-3305 ◽  
Author(s):  
Linli Zhou ◽  
Kun Yang ◽  
April Carpenter ◽  
Richard A. Lang ◽  
Thomas Andl ◽  
...  

Active Wnt/β-catenin signaling in the dermal papilla (DP) is required for postnatal hair cycling. In addition, maintenance of the hair-inducing ability of DP cells in vitro requires external addition of Wnt molecules. However, whether DP cells are a critical source of Wnt ligands and induce both autocrine and paracrine signaling cascades to promote adult hair follicle growth and regeneration remains elusive. To address this question, we generated an animal model that allows inducible ablation of Wntless (Wls), a transmembrane Wnt exporter protein, in CD133-positive (CD133+) DP cells. CD133+ cells have been shown to be a specific subpopulation of cells in the DP, which possesses the hair-inducing capability. Here, we show that ablation of Wls expression in CD133+ DP cells results in a shortened period of postnatal hair growth. Mutant hair follicles were unable to enter full anagen (hair growth stage) and progressed toward a rapid regression. Notably, reduced size of the DP and decreased expression of anagen DP marker, versican, were observed in hair follicles when CD133+ DP cells lost Wls expression. Further analysis showed that Wls-deficient CD133+ DP cells led to reduced proliferation and differentiation in matrix keratinocytes and melanocytes that are needed for the generation of the hair follicle structure and a pigmented hair shaft. These findings clearly demonstrate that Wnt ligands produced by CD133+ DP cells play an important role in postnatal hair growth by maintaining the inductivity of DP cells and mediating the signaling cross-talk between the mesenchyme and the epithelial compartment.


2020 ◽  
Vol 21 (16) ◽  
pp. 5672
Author(s):  
Kyung-Eun Ku ◽  
Nahyun Choi ◽  
Jong-Hyuk Sung

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.


2020 ◽  
Vol 21 (12) ◽  
pp. 4553
Author(s):  
Sung Min Kim ◽  
Jung-Il Kang ◽  
Hoon-Seok Yoon ◽  
Youn Kyung Choi ◽  
Ji Soo Go ◽  
...  

The hair follicle goes through repetitive cycles including anagen, catagen, and telogen. The interaction of dermal papilla cells (DPCs) and keratinocytes regulates the hair cycle and hair growth. Humanin was discovered in the surviving brain cells of patients with Alzheimer’s disease. HNG, a humanin analogue, activates cell growth, proliferation, and cell cycle progression, and it protects cells from apoptosis. This study was performed to investigate the promoting effect and action mechanisms of HNG on hair growth. HNG significantly increased DPC proliferation. HNG significantly increased hair shaft elongation in vibrissa hair follicle organ culture. In vivo experiment showed that HNG prolonged anagen duration and inhibited hair follicle cell apoptosis, indicating that HNG inhibited the transition from the anagen to catagen phase mice. Furthermore, HNG activated extracellular signal-regulated kinase (Erk)1/2, Akt, and signal transducer and activator of transcription (Stat3) within minutes and up-regulated vascular endothelial growth factor (VEGF) levels on DPCs. This means that HNG could induce the anagen phase longer by up-regulating VEGF, which is a Stat3 target gene and one of the anagen maintenance factors. HNG stimulated the anagen phase longer with VEGF up-regulation, and it prevented apoptosis by activating Erk1/2, Akt, and Stat3 signaling.


Development ◽  
1976 ◽  
Vol 36 (3) ◽  
pp. 597-607
Author(s):  
R. D. Young ◽  
R. F. Oliver

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.


Development ◽  
2000 ◽  
Vol 127 (11) ◽  
pp. 2421-2432 ◽  
Author(s):  
M.H. Lin ◽  
C. Leimeister ◽  
M. Gessler ◽  
R. Kopan

Little is known about the mechanisms underlying the generation of various cell types in the hair follicle. To investigate the role of the Notch pathway in this process, transgenic mice were generated in which an active form of Notch1 (Notch(DeltaE)) was overexpressed under the control of the mouse hair keratin A1 (MHKA1) promoter. MHKA-Notch(DeltaE) is expressed only in one precursor cell type of the hair follicle, the cortex. Transgenic mice could be easily identified by the phenotypes of curly whiskers and wavy, sheen pelage hair. No effects of activated Notch on proliferation were detected in hair follicles of the transgenic mice. We find that activating Notch signaling in the cortex caused abnormal differentiation of the medulla and the cuticle, two neighboring cell types that did not express activated Notch. We demonstrate that these non-autonomous effects are likely caused by cell-cell interactions between keratinocytes within the hair follicle and that Notch may function in such interactions either by directing the differentiation of follicular cells or assisting cells in interpreting a gradient emanating from the dermal papilla.


2002 ◽  
Vol 50 (6) ◽  
pp. 751-766 ◽  
Author(s):  
Eva M. J. Peters ◽  
Desmond J. Tobin ◽  
Natasha Botchkareva ◽  
Marcus Maurer ◽  
Ralf Paus

Disruption of the c-Kit/stem cell factor (SCF) signaling pathway interferes with the survival, migration, and differentiation of melanocytes during generation of the hair follicle pigmentary unit. We examined c-Kit, SCF, and S100 (a marker for precursor melanocytic cells) expression, as well as melanoblast/melanocyte ultrastructure, in perinatal C57BL/6 mouse skin. Before the onset of hair bulb melanogenesis (i.e., stages 0–4 of hair follicle morphogenesis), strong c-Kit immunoreactivity (IR) was seen in selected non-mela-nogenic cells in the developing hair placode and hair plug. Many of these cells were S100-IR and were ultrastructurally identified as melanoblasts with migratory appearance. During the subsequent stages (5 and 6), increasingly dendritic c-Kit-IR cells successively invaded the hair bulb, while S100-IR gradually disappeared from these cells. Towards the completion of hair follicle morphogenesis (stages 7 and 8), several distinct follicular melanocytic cell populations could be defined and consisted broadly of (a) undifferentiated, non-pigmented c-Kit-negative melanoblasts in the outer root sheath and bulge and (b) highly differentiated melanocytes adjacent to the hair follicle dermal papilla above Auber's line. Widespread epithelial SCF-IR was seen throughout hair follicle morphogenesis. These findings suggest that melanoblasts express c-Kit as a prerequisite for migration into the SCF-supplying hair follicle epithelium. In addition, differentiated c-Kit-IR melanocytes target the bulb, while non-c-Kit-IR melanoblasts invade the outer root sheath and bulge in fully developed hair follicles.


1973 ◽  
Vol 21 (2) ◽  
pp. 153 ◽  
Author(s):  
AG Lyne ◽  
DE Hollis

Development of horns has been studied in 20 foetuses ranging in age from 55 to 144 days of gestation, and in 16 lambs, ranging in age from birth to 42 days. Samples from one adult have also been examined. An increase in the thickness of the epidermis appears to be the first indication of horn development, recognizable in a 75-day-old male foetus and in an 84-day-old female foetus. Primary hair follicles develop in the horn region and produce emerging hairs, but these follicles later degenerate and disappear. The sweat glands and sebaceous glands formed in association with these follicles also degenerate, usually after hair growth has ceased. Fusion of primary follicles is a common feature in the horn growing skin, particularly before hair formation; a common connective tissue sheath surrounds the lower parts of these fused follicles. No secondary follicles are formed in the horn region but some branching of the primary follicles has been observed. By 118 days of gestation the epidermis in the horn region becomes greatly thickened, with very long dermal papillae which are well vascularized and innervated. Medulla-like columns of cells are formed above each dermal papilla and these cells keratinize later than the cells between the columns. These medullary cells remain in contact with each other longer than do the other cells of the horny sheath. Numerous arteriovenous anastomoses, which develop at two levels in the dermis of the horn region, are in continuity with capillaries which enter the dermal papillae of the epidermis. An outgrowth of bone from the frontal region of the skull, which later becomes the bony core of the horn, is first seen in a male foetus at 118 days. Acetylcholinesterase-positive branched cells (Langerhans cells), present in the lower part of the thick epidermis of developing horns, are not discernible in fully formed horns.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1155
Author(s):  
Jiyu Hyun ◽  
Jisoo Im ◽  
Sung-Won Kim ◽  
Han Young Kim ◽  
Inwoo Seo ◽  
...  

Restoring hair follicles by inducing the anagen phase is a promising approach to prevent hair loss. Hair follicle dermal papilla cells (HFDPCs) play a major role in hair growth via the telogen-to-anagen transition. The therapeutic effect of Morus alba activates β-catenin in HFDPCs, thereby inducing the anagen phase. The HFDPCs were treated with M. alba root extract (MARE) to promote hair growth. It contains chlorogenic acid and umbelliferone and is not cytotoxic to HFDPCs at a concentration of 20%. It was demonstrated that a small amount of MARE enhances growth factor secretion (related to the telogen-to-anagen transition). Activation of β-catenin was observed in MARE-treated HFDPCs, which is crucial for inducing the anagen phase. The effect of conditioned medium derived from MARE-treated HFDPCs on keratinocytes and endothelial cells was also investigated. The findings of this study demonstrate the potency of MARE in eliciting the telogen-to-anagen transition.


2015 ◽  
Vol 1 (9) ◽  
pp. e1500973 ◽  
Author(s):  
Sivan Harel ◽  
Claire A. Higgins ◽  
Jane E. Cerise ◽  
Zhenpeng Dai ◽  
James C. Chen ◽  
...  

Several forms of hair loss in humans are characterized by the inability of hair follicles to enter the growth phase (anagen) of the hair cycle after being arrested in the resting phase (telogen). Current pharmacologic therapies have been largely unsuccessful in targeting pathways that can be selectively modulated to induce entry into anagen. We show that topical treatment of mouse and human skin with small-molecule inhibitors of the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway results in rapid onset of anagen and subsequent hair growth. We show that JAK inhibition regulates the activation of key hair follicle populations such as the hair germ and improves the inductivity of cultured human dermal papilla cells by controlling a molecular signature enriched in intact, fully inductive dermal papillae. Our findings open new avenues for exploration of JAK-STAT inhibition for promotion of hair growth and highlight the role of this pathway in regulating the activation of hair follicle stem cells.


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