Sox2 in the Dermal Papilla Niche Controls Hair Growth by Fine-Tuning BMP Signaling in Differentiating Hair Shaft Progenitors

Clavel, Carlos; Grisanti, Laura; Zemla, Roland; Rezza, Amélie; Barros, Rita; Sennett, Rachel; Mazloom, Amin R.; Chung, Chi‐Yeh; Cai, Xiaoqiang; Cai, Chen-Leng; Pevny, Larysa; Nicolis, Silvia K.; Ma’ayan, Avi; Rendl, Michael

doi:10.1016/j.devcel.2012.10.013

Cited by 142 publications

(138 citation statements)

References 55 publications

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“…Unexpectedly, conditional ablation of Sox2 in E14.5 DC allowed DPs and HFs to form. The resulting phenotype was modest and restricted to these three hair types (Clavel et al, 2012;Lesko et al, 2013). This suggests that expression of Sox2 is dispensable for dermal papilla specification, even if it could be important for some aspects of its function.…”

Section: Introductionmentioning

confidence: 87%

Dominant-negative Sox18 function inhibits dermal papilla maturation and differentiation in all murine hair types

et al. 2017

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SOX family proteins SOX2 and SOX18 have been reported as being essential in determining hair follicle type; however, the role they play during development remains unclear. Here, we demonstrate that Sox18 regulates the normal differentiation of the dermal papilla of all hair types. In guard ( primary) hair dermal condensate (DC) cells, we identified transient Sox18 in addition to SOX2 expression at E14.5, which allowed fate tracing of primary DC cells until birth. Similarly, expression of Sox18 was detected in the DC cells of secondary hairs at E16.5 and in tertiary hair at E18.5. Dominant-negative Sox18 mutation (opposum) did not prevent DC formation in any hair type. However, it affected dermal papilla differentiation, restricting hair formation especially in secondary and tertiary hairs. This Sox18 mutation also prevented neonatal dermal cells or dermal papilla spheres from inducing hair in regeneration assays. Microarray expression studies identified WNT5A and TNC as potential downstream effectors of SOX18 that are important for epidermal WNT signalling. In conclusion, SOX18 acts as a mesenchymal molecular switch necessary for the formation and function of the dermal papilla in all hair types.

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Section: Introductionmentioning

confidence: 87%

Dominant-negative Sox18 function inhibits dermal papilla maturation and differentiation in all murine hair types

et al. 2017

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“…Sox2 has important roles in the development of several endodermal tissues, such as the trachea (Xie et al, 2014) stomach and gut (Que et al, 2007), as well as in ectodermal tissues including the anterior pituitary (Jayakody et al, 2012), lens epithelium (Taranova et al, 2006), tongue epithelium and hair follicles (Clavel et al, 2012). Sox2 was recently identified as a marker for DESCs.…”

Section: Introductionmentioning

confidence: 99%

“…This structure acts as a signaling center to control stem cell fate (Clavel et al, 2012;Lane et al, 2014;Spradling et al, 2001). The precise and timely regulation of stem cell renewal and differentiation is essential for tissue formation, growth and homeostasis over the course of a lifetime (Moore et al, 2006), but the molecular mechanisms underpinning this regulation are variable and dependent on tissuespecific signaling and transcription factors.…”

Section: Introductionmentioning

confidence: 99%

Sox2 and Lef-1 interact with Pitx2 to regulate incisor development and stem cell renewal

et al. 2016

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Sox2 marks dental epithelial stem cells (DESCs) in both mammals and reptiles, and in this article we demonstrate several Sox2 transcriptional mechanisms that regulate dental stem cell fate and incisor growth. Conditional Sox2 deletion in the oral and dental epithelium results in severe craniofacial defects, including impaired dental stem cell proliferation, arrested incisor development and abnormal molar development. The murine incisor develops initially but is absorbed independently of apoptosis owing to a lack of progenitor cell proliferation and differentiation. Tamoxifen-induced inactivation of Sox2 demonstrates the requirement of Sox2 for maintenance of the DESCs in adult mice. Conditional overexpression of Lef-1 in mice increases DESC proliferation and creates a new labial cervical loop stem cell compartment, which produces rapidly growing long tusk-like incisors, and Lef-1 epithelial overexpression partially rescues the tooth arrest in Sox2 conditional knockout mice. Mechanistically, Pitx2 and Sox2 interact physically and regulate Lef-1, Pitx2 and Sox2 expression during development. Thus, we have uncovered a Pitx2-Sox2-Lef-1 transcriptional mechanism that regulates DESC homeostasis and dental development.

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“…Unexpectedly, conditional ablation of Sox2 in the DC at E14.5 has allowed DP and hair follicles to form. The resulting phenotype was modest and restricted to these three hair types (Clavel et al, 2012;Lesko et al, 2013). This suggests that expression of Sox2 is dispensable for DP specification even if it could be important for some aspects of its function.…”

Section: Introductionmentioning

confidence: 88%

“…An earlier study has also demonstrated that Sox2 ablation in the DC does not affect hair follicle formation. The study also suggested that Sox2 negatively regulates BMP signalling within the hair follicle, and its absence results in an inability for matrix progenitor cells to migrate to the hair shaft as they differentiate (Clavel et al, 2012).…”

Section: Sox2 and Sox18 In Dermal Papilla Specificationmentioning

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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Sox2 in the Dermal Papilla Niche Controls Hair Growth by Fine-Tuning BMP Signaling in Differentiating Hair Shaft Progenitors

Cited by 142 publications

References 55 publications

Dominant-negative Sox18 function inhibits dermal papilla maturation and differentiation in all murine hair types

Dominant-negative Sox18 function inhibits dermal papilla maturation and differentiation in all murine hair types

Sox2 and Lef-1 interact with Pitx2 to regulate incisor development and stem cell renewal

Mesenchymal-epidermal interactions in hair follicle cycling and regeneration

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