Genetic interplays between Msx2 and Foxn1 are required for Notch1 expression and hair shaft differentiation

Cai, Jing; Lee, Jonghyeob; Kopan, Raphael; Ma, Liang

doi:10.1016/j.ydbio.2008.11.021

Cited by 68 publications

(80 citation statements)

References 61 publications

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“…Notch signaling acts by blocking cell differentiation, which maintains the competence of undifferentiated cells [88,89] in both the developing tooth and the HF to respond to inductive signals that determine their developmental fate [87,90]. Based on expression studies in the HF, Notch may be a competence factor, as its pattern of expression in the HF appears to be restricted to cells that have left the proliferative pool but have yet to terminally differentiate [91,92].…”

Section: Molecular Control Of Hair Follicle Development and Cyclingmentioning

confidence: 99%

Biology of Human Hair: Know Your Hair to Control It

Araújo

Fernandes

Cavaco‐Paulo

et al. 2010

Advances in Biochemical Engineering/Biotechnology

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Hair can be engineered at different levels-its structure and surfacethrough modification of its constituent molecules, in particular proteins, but also the hair follicle (HF) can be genetically altered, in particular with the advent of siRNA-based applications. General aspects of hair biology are reviewed, as well as the most recent contributions to understanding hair pigmentation and the regulation of hair development. Focus will also be placed on the techniques developed specifically for delivering compounds of varying chemical nature to the HF, indicating methods for genetic/biochemical modulation of HF components for the treatment of hair diseases. Finally, hair fiber structure and chemical characteristics will be discussed as targets for keratin surface functionalization.

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Section: Molecular Control Of Hair Follicle Development and Cyclingmentioning

confidence: 99%

Biology of Human Hair: Know Your Hair to Control It

Araújo

Fernandes

Cavaco‐Paulo

et al. 2010

Advances in Biochemical Engineering/Biotechnology

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“…2C), were significantly downregulated following TSH administration. Since MSX2 serves as a major transcription factor that regulates hair keratin expression [7], analysis of MSX2 expression was also performed. Indeed, TSH downregulated MSX2 transcription in human anagen HFs in situ (Fig.…”

mentioning

confidence: 99%

“…These include members of the Wnt/β-catenin pathway and of the TGF-β family which control MSX2, FOXN1 and HOXC13 activity [1,2,7,11,12].…”

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confidence: 99%

TSH is a novel neuroendocrine regulator of selected keratins in the human hair follicle

Ramot

Zhang

Bı́ró

et al. 2011

Journal of Dermatological Science

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2Keratins and keratin-associated proteins (KAPs) constitute the major structural protein components of the hair. Regulation of their expression is critical for proper hair follicle (HF) structure and function [1]. Therefore, it is important to fully elucidate the controls that regulate keratin expression. Although it is accepted that the expression of selected keratin genes underlies endocrine controls [1,2], our understanding of the complex regulation of keratin expression remains rather fragmentary. To better elucidate this regulation, human skin and HF organ culture offer an instructive, physiologically relevant research tool [1,3].In particular, very little is known on the neuroendocrine controls of keratin transcription. The importance of the latter is highlighted by the recent discovery that the "pituitary" neuropeptide hormone, prolactin, which is also expressed by human HFs, potently regulates the expression of selected human keratins on the gene and protein level [3]. Moreover, microarray analyses had provided first clues that thyroid stimulating hormone (TSH) and its proximal regulator in the hypothalamic-pituitary-thyroid axis, thyrotropin-releasing hormone (TRH), might operate as previously unsuspected modulators of human hair keratin and KAP gene transcription in situ [4][5][6]. Also, we had recently found that TSH upregulates keratin K5 gene expression and protein synthesis as well as K14 transcription in human epidermis [4]. Therefore, we have asked whether TSH operates as a novel neuroendocrine regulator of human keratins in situ, using microdissected, organ-cultured human scalp HFs as a physiologically and clinically relevant assay systems [3][4][5]. This was complemented by studying the effect of TSH on keratin expression in cultured human outer root sheath (ORS) keratinocytes (KCs).Anagen VI HFs were isolated from normal frontotemporal scalp skin obtained after written informed consent from three healthy females undergoing routine face-lift surgery, as 3 previously described [4,5], adhering to Helsinki guidelines and under a licence from the ethics committee of the University of Lübeck. HF mRNA extracts from one female patient were subjected to quantitative real time PCR (qPCR) for selected hair keratin genes after 24 hrs treatment with TSH (100 mU ml -1 ) or vehicle. For immunohistochemical analysis, isolatedHFs from additional two female patients were organ cultured for 6 days as described previously [3,4], and expression of keratins K6, K14, K17, K31, K32, K85 and MSX-2 was studied with our previously published basic immunohistology protocols [3,4] ( These qPCR analyses demonstrated that TSH downregulated transcription of KRT31 and KRT32 genes (Fig. 1A). In these qPCR analyses, KRT35 transcription was largely unaffected by TSH. Instead, transcription of its type II counterpart keratin gene, KRT85 [2], was downregulated (Fig. 1A). 4Immunohistochemical studies on TSH treated HFs confirmed the downregulation of the hair keratins also at the protein level ( Fig. 2A-C): K31 immunoreactivity, loc...

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“…Again, the Wnt signalling pathway is implicated, however a prominent role in hair shaft differentiation has been attributed to the homeobox (HOX) transcription factor, HOXC13, and its upregulation of Forkhead box N1 (Foxn1) Potter et al, 2011). Foxn1 is also described to be an activator of Notch1 expression, and Notch signalling in combination with msh HOX 2 (Msx2) is suggested to play an essential role in hair cortex and medulla differentiation (Cai et al, 2009).…”

Section: Embryonic Hair Follicle Developmentmentioning

confidence: 99%

Mesenchymal-epidermal interactions in hair follicle cycling and regeneration

Legrand¹

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The hair follicle is an important skin appendage that arises during development from complex reciprocal signalling between the epidermis and dermis. The multiple epidermal layers of the hair follicle are known to be under the control of the mesenchymal component, the dermal papilla (DP), which has been described as the key regulator of hair follicle induction and maintenance. The hair follicle has elicited interest as a model system for the investigation of tissue and organ regeneration due to its ability to regenerate completely throughout the life of a mammal. This characteristic is attributed to the reservoir of stem cells within the hair follicle, which is modulated by the DP.Although it is known that the DP is central to regulation of the hair follicle, mediators of its signalling are incompletely understood. Potential mediators of DP activity continue to emerge, two of which include the SoxF transcription factor, Sox18, and the transcription factor, STAT5. Sox18 has been implicated in hair type specification by the DP; however, its expression and function remains unclear. STAT5 has been shown in microarray analyses of the DP to be specifically expressed and upregulated, while studies involving STAT5 genetic knockouts display a hair phenotype. More recently, STAT5 has been implicated in autoimmune conditions affecting the hair follicle such as alopecia areata.To investigate further the role of STAT5 in the DP, I have hypothesised that STAT5 plays a key role in the DP's hair follicle inductive properties and regulation of cycling.STAT5 activation in the DP was characterised through immunofluorescence staining of mouse back skin at various stages of hair follicle development and cycling. Back skin was obtained from Topflash transgenic mice, a canonical Wnt reporter transgenic mouse driving luciferase expression, using β-catenin activity to monitor hair cycling via live bioluminescence imaging. While embryonic skin did not display any activation of STAT5, during postnatal hair follicle development (P0-P19), the majority of phospho-STAT5 positive DP were present within telogen phase, to a lesser extent within catagen and not at all during anagen. Adult skin showed phospho-STAT5 activation beginning in late catagen and persisting through to early anagen.Characterisation of SOCS2 by immunofluorescence, a downstream STAT5 transcriptional target, showed expression corresponding to the chronology of phospho-STAT5 activity.Hair regeneration assays were performed with DP cells using SKP culture with STAT5 activity modified through adenovirus constructs. SKPs derived from C57BL/6 neonates and STAT5 lox/lox neonates were transduced with STAT5A/B constitutively-active and crerecombinase constructs, respectively. These transduced SKPs were then used in patch assay experiments and DP formation was quantified using a green fluorescent protein ii (GFP) reporter. SKPs transduced with constitutively-active STAT5 were significantly better at forming hair follicle DP than control SKPs transduced with GFP alone. SKPs with...

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Genetic interplays between Msx2 and Foxn1 are required for Notch1 expression and hair shaft differentiation

Cited by 68 publications

References 61 publications

Biology of Human Hair: Know Your Hair to Control It

Biology of Human Hair: Know Your Hair to Control It

TSH is a novel neuroendocrine regulator of selected keratins in the human hair follicle

Mesenchymal-epidermal interactions in hair follicle cycling and regeneration

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