Foxn1 is required for tissue assembly and desmosomal cadherin expression in the hair shaft

Johns, Sarah Anne; Soullier, Stephan; Rashbass, Penny; Cunliffe, Vincent T.

doi:10.1002/dvdy.20278

Cited by 31 publications

(38 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A number of transcriptional targets of FoxN1 have been reported previously, including Phospholipase C-d1 (Plcd1) (Janes et al 2004;Nakamura et al 2008) and desmocollin 2 (DSC2) (Johns et al 2005). Similar downmodulation of these genes, as well as trichohyalin, was found in cultured hair follicles with siRNA-mediated knockdown of FoxN1 expression as in hair follicles derived from mice with the RBP-Jk deletion (Fig.…”

Section: Functional Rescue Of Defective Rbp-jksupporting

confidence: 71%

Control of hair follicle cell fate by underlying mesenchyme through a CSL–Wnt5a–FoxN1 regulatory axis

Hu¹,

Lefort²,

Qiu³

et al. 2010

Genes Dev.

View full text Add to dashboard Cite

Epithelial–mesenchymal interactions are key to skin morphogenesis and homeostasis. We report that maintenance of the hair follicle keratinocyte cell fate is defective in mice with mesenchymal deletion of the CSL/RBP-Jκ gene, the effector of “canonical” Notch signaling. Hair follicle reconstitution assays demonstrate that this can be attributed to an intrinsic defect of dermal papilla cells. Similar consequences on hair follicle differentiation result from deletion of Wnt5a, a specific dermal papilla signature gene that we found to be under direct Notch/CSL control in these cells. Functional rescue experiments establish Wnt5a as an essential downstream mediator of Notch–CSL signaling, impinging on expression in the keratinocyte compartment of FoxN1, a gene with a key hair follicle regulatory function. Thus, Notch/CSL signaling plays a unique function in control of hair follicle differentiation by the underlying mesenchyme, with Wnt5a signaling and FoxN1 as mediators.

show abstract

Section: Functional Rescue Of Defective Rbp-jksupporting

confidence: 71%

Control of hair follicle cell fate by underlying mesenchyme through a CSL–Wnt5a–FoxN1 regulatory axis

Hu¹,

Lefort²,

Qiu³

et al. 2010

Genes Dev.

View full text Add to dashboard Cite

show abstract

“…S5). We also examined other genes, which were known to be expressed in the cortex (Foxn1, Krt35, Krt85) (9,10,19), and matrix (Hoxc13, Msx2) (20,21). None, however, showed a significant reduction in Sox21 Ϫ/Ϫ mice (Fig.…”

Section: Sox21 Is a Master Regulator Of Keratin Gene Network In The Cuhmentioning

confidence: 99%

The disruption of Sox21-mediated hair shaft cuticle differentiation causes cyclic alopecia in mice

Kiso¹,

Tanaka

Saba³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Hair is maintained through a cyclic process that includes periodic regeneration of hair follicles in a stem cell-dependent manner. Little is known, however, about the cellular and molecular mechanisms that regulate the layered differentiation of the hair follicle. We have established a mutant mouse with a cyclic alopecia phenotype resulting from the targeted disruption of Sox21, a gene that encodes a HMG-box protein. These mice exhibit progressive hair loss after morphogenesis of the first hair follicle and become completely nude in appearance, but then show hair regrowth. Sox21 is expressed in the cuticle layer and the progenitor cells of the hair shaft in both mouse and human. The lack of this gene results in a loss of the interlocking structures required for anchoring the hair shaft in the hair follicle. Furthermore, the expression of genes encoding the keratins and keratin binding proteins in the hair shaft cuticle are also specifically down-regulated in the Sox21-null mouse. These results indicate that Sox21 is a master regulator of hair shaft cuticle differentiation and shed light on the possible causes of human hair disorders.hair follicle ͉ keratin ͉ epidermal hyperplasia

show abstract

“…How could Rac1 regulate structure formation of the hair shaft? It is known that cells of the medulla are tethered to the cortex by cell-cell contacts that contain Dsc2 (Johns et al, 2005;Cai et al, 2009). Considering the role of Rac1 in cell-cell contact formation in vitro (Braga et al, 1997;Takaishi et al, 1997), it is possible that the absence of Rac1 prevents the formation of these cortex-medulla contacts.…”

Section: Discussionmentioning

confidence: 99%

“…Medulla cells express desmocollin 2 (Dsc2), whereas cortex cells express desmoglein 4 (Dsg4) (Kurzen et al, 2001;Bazzi et al, 2006;Bazzi et al, 2009). We therefore stained skin sections with an antibody against desmocollin 2 (Dsc2), a desmosomal cadherin that is expressed by medulla cells and is localized to the so-called A-ridges (Trigg, 1972;Johns et al, 2005), and with the antibody AE-13 that stains keratins of the hair cortex. As has been described previously (Lynch et al, 1986), staining of normal hair with AE-13 detected small hair-keratin-containing spikes of cortex cells that protrude into the medulla space.…”

Section: Abnormal Hair Structure and Medulla Cell Organization In Resmentioning

confidence: 99%

“…These pseudopodia are subsequently shed as cytoplasm-containing vesicles, resulting in the formation of a groove in medulla cells that is filled with tonofilament bundles originating from cortex cells (Morioka, 2005). The border between cortex and medulla cells is decorated with the desmosomal cadherin desmocollin 2 (Dsc2 protein) (Johns et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A function for Rac1 in the terminal differentiation and pigmentation of hair

Behrendt

Klatte

Pofahl

et al. 2012

Journal of Cell Science

View full text Add to dashboard Cite

SummaryThe small GTPase Rac1 is ubiquitously expressed in proliferating and differentiating layers of the epidermis and hair follicles. Previously, Rac1 was shown to regulate stem cell behaviour in these compartments. We have asked whether Rac1 has, in addition, a specific, stem-cell-independent function in the regulation of terminal hair follicle differentiation. To address this, we have expressed a constitutively active mutant of Rac1, L61Rac1, only in the basal epidermal layer and outer root sheath of mice possessing an epidermisspecific deletion of endogenous Rac1, which experience severe hair loss. The resulting 'rescue' mice exhibited a hair coat throughout their lives. Therefore, expression of Rac1 activity in the keratin-14-positive compartment of the skin is sufficient for the formation of hair follicles and hair in normal quantities. The quality of hair formed in rescue mice was, however, not normal. Rescue mice showed a grey, dull hair coat, whereas that of wild-type and L61Rac1-transgenic mice was black and shiny. Hair analysis in rescue mice revealed altered structures of the hair shaft and the cuticle and disturbed organization of medulla cells and pigment distribution. Disorganization of medulla cells correlates with the absence of cortical, keratin-filled spikes that normally protrude from the cortex into the medulla. The desmosomal cadherin Dsc2, which normally decorates these protrusions, was found to be reduced or absent in the hair of rescue mice. Our study demonstrates regulatory functions for Rac1 in the formation of hair structure and pigmentation and thereby identifies, for the first time, a role for Rac1 in terminal differentiation.

show abstract

Foxn1 is required for tissue assembly and desmosomal cadherin expression in the hair shaft

Cited by 31 publications

References 33 publications

Control of hair follicle cell fate by underlying mesenchyme through a CSL–Wnt5a–FoxN1 regulatory axis

Control of hair follicle cell fate by underlying mesenchyme through a CSL–Wnt5a–FoxN1 regulatory axis

The disruption of Sox21-mediated hair shaft cuticle differentiation causes cyclic alopecia in mice

A function for Rac1 in the terminal differentiation and pigmentation of hair

Contact Info

Product

Resources

About