p63 in epithelial development

Candi, Eleonora; Cipollone, Rita; Cervo, Pia Rivetti di Val; Gonfloni, Stefania; Melino, Gerry; Knight, Richard

doi:10.1007/s00018-008-8119-x

Cited by 121 publications

(109 citation statements)

References 54 publications

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“…The development of the skin starts with the commitment of singlelayered surface ectoderm to stratification controlled by the transcription factor TRP63 (Candi et al, 2008(Candi et al, , 2007, followed by the terminal differentiation of epidermal keratinocytes (Blanpain et al, 2006). The induction of hair follicle formation is initiated by reciprocal interactions between epidermal keratinocytes and folliculogenic dermal papilla cells mediated by molecular signaling pathways, notably canonical Wnt signaling (Schmidt-Ullrich and Paus, 2005).…”

Section: Introductionmentioning

confidence: 99%

Intraflagellar transport 27 is essential for hedgehog signaling but dispensable for ciliogenesis during hair follicle morphogenesis

Yang

Eguether

et al. 2015

Development

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Hair follicle morphogenesis requires precisely controlled reciprocal communications, including hedgehog (Hh) signaling. Activation of the Hh signaling pathway relies on the primary cilium. Disrupting ciliogenesis results in hair follicle morphogenesis defects due to attenuated Hh signaling; however, the loss of cilia makes it impossible to determine whether hair follicle phenotypes in these cilia mutants are caused by the loss of cilia, disruption of Hh signaling, or a combination of these events. In this study, we characterized the function of Ift27, which encodes a subunit of intraflagellar transport (IFT) complex B. Hair follicle morphogenesis of Ift27-null mice was severely impaired, reminiscent of phenotypes observed in cilia and Hh mutants. Furthermore, the Hh signaling pathway was attenuated in Ift27 mutants, which was in association with abnormal ciliary trafficking of SMO and GLI2, and impaired processing of Gli transcription factors; however, formation of the ciliary axoneme was unaffected. The ciliary localization of IFT25 (HSPB11), the binding partner of IFT27, was disrupted in Ift27 mutant cells, and Ift25-null mice displayed hair follicle phenotypes similar to those of Ift27 mutants. These data suggest that Ift27 and Ift25 operate in a genetically and functionally dependent manner during hair follicle morphogenesis. This study suggests that the molecular trafficking machineries underlying ciliogenesis and Hh signaling can be segregated, thereby providing important insights into new avenues of inhibiting Hh signaling, which might be adopted in the development of targeted therapies for Hh-dependent cancers, such as basal cell carcinoma.

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Section: Introductionmentioning

confidence: 99%

Intraflagellar transport 27 is essential for hedgehog signaling but dispensable for ciliogenesis during hair follicle morphogenesis

Yang

Eguether

et al. 2015

Development

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“…TAC cells then embark on differentiation programs to generate the spinous, granular, and cornified layers in the IFE or the different lineages of mature HFs (12)(13)(14). Several essential molecular circuitries that orchestrate ESC maintenance, including p63-, BMP-, TGF-β-, Wnt/β-catenin-, and Notchinitiated signaling cascades, have been described (12,15,16).…”

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confidence: 99%

Transcription factor E4F1 is essential for epidermal stem cell maintenance and skin homeostasis

Lacroix

Caramel

Goguet-Rubio

et al. 2010

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

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A growing body of evidence suggests that the multifunctional protein E4F1 is involved in signaling pathways that play essential roles during normal development and tumorigenesis. We generated E4F1 conditional knockout mice to address E4F1 functions in vivo in newborn and adult skin. E4F1 inactivation in the entire skin or in the basal compartment of the epidermis induces skin homeostasis defects, as evidenced by transient hyperplasia in the interfollicular epithelium and alteration of keratinocyte differentiation, followed by loss of cellularity in the epidermis and severe skin ulcerations. E4F1 depletion alters clonogenic activity of epidermal stem cells (ESCs) ex vivo and ends in exhaustion of the ESC pool in vivo, indicating that the lesions observed in the E4F1 mutant skin result, at least in part, from cell-autonomous alterations in ESC maintenance. The clonogenic potential of E4F1 KO ESCs is rescued by Bmi1 overexpression or by Ink4a/Arf or p53 depletion. Skin phenotype of E4F1 KO mice is also delayed in animals with Ink4a/Arf and E4F1 compound gene deficiencies. Our data identify a regulatory axis essential for ESC-dependent skin homeostasis implicating E4F1 and the Bmi1–Arf–p53 pathway.

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“…In addition, POU-domain proteins (transcription factors that contain a bipartite DNA-binding domain known as the POU domain) expressed in the epidermis, such as Oct1, Skn1a/i and Oct6, bind in vitro to two specific recognition elements within the FLG promoter and exert their effects by either stimulating or antagonising the Jun-dependent activity of the promoter (Jang et al, 2000). The transcription factor p63 has been shown to be essential for epidermal development and exists as multiple isoforms, which arise as a result of alternative promoter usage (Candi et al, 2008). These isoforms are expressed differentially during keratinocyte differentiation.…”

Section: Control Of Flg Gene Expressionmentioning

confidence: 99%

Filaggrin in the frontline: role in skin barrier function and disease

Sandilands

Sutherland

Irvine

et al. 2009

Journal of Cell Science

703

685

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Recently, loss-of-function mutations in FLG, the human gene encoding profilaggrin and filaggrin, have been identified as the cause of the common skin condition ichthyosis vulgaris (which is characterised by dry, scaly skin). These mutations, which are carried by up to 10% of people, also represent a strong genetic predisposing factor for atopic eczema, asthma and allergies. Profilaggrin is the major component of the keratohyalin granules within epidermal granular cells. During epidermal terminal differentiation, the ~400 kDa profilaggrin polyprotein is dephosphorylated and rapidly cleaved by serine proteases to form monomeric filaggrin (37 kDa), which binds to and condenses the keratin cytoskeleton and thereby contributes to the cell compaction process that is required for squame biogenesis. Within the squames, filaggrin is citrullinated, which promotes its unfolding and further degradation into hygroscopic amino acids, which constitute one element of natural moisturising factor. Loss of profilaggrin or filaggrin leads to a poorly formed stratum corneum (ichthyosis), which is also prone to water loss (xerosis). Recent human genetic studies strongly suggest that perturbation of skin barrier function as a result of reduction or complete loss of filaggrin expression leads to enhanced percutaneous transfer of allergens. Filaggrin is therefore in the frontline of defence, and protects the body from the entry of foreign environmental substances that can otherwise trigger aberrant immune responses.

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p63 in epithelial development

Cited by 121 publications

References 54 publications

Intraflagellar transport 27 is essential for hedgehog signaling but dispensable for ciliogenesis during hair follicle morphogenesis

Intraflagellar transport 27 is essential for hedgehog signaling but dispensable for ciliogenesis during hair follicle morphogenesis

Transcription factor E4F1 is essential for epidermal stem cell maintenance and skin homeostasis

Filaggrin in the frontline: role in skin barrier function and disease

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