Fiona M Watt

..The work is discussed in the broader context of Ihh expression and function in epithelia and the different ways in which the Hh and Wnt pathways interact...

..In adult epidermis, Myc stimulates exit from the stem cell compartment, decreasing cell adhesion and, by an unknown mechanism, triggering proliferation of transit-amplifying cells...

..GLI1-dependent transcription is positively regulated by DYRK1A, which is reported to bind HAN11. HAN11 is the human homologue of AN11, which controls flavonoid synthesis in plants...

..beta-catenin stimulates Notch signalling by inducing Jag1 transcription. We conclude that the Notch pathway acts downstream of the Wnt/beta-catenin pathway to determine epidermal cell fate...

..We conclude that a pleiotropic regulator of cell adhesion and the cytoskeleton plays a critical role in controlling exit from the stem cell niche and propose that Rac and Myc represent a global stem cell regulatory axis...

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..These results establish a role for FOXN1 in initiation of terminal differentiation and implicate Akt in subsequent events...

..These data suggest that activation of MEK1 downstream of beta1 integrins plays an important role in epidermal hyperproliferation and skin inflammation...

..Lrig1 acted in part by negatively regulating the Myc promoter. We propose that Lrig1 maintains epidermal stem cells in a quiescent nondividing state, and that Lrig1 down-regulation triggers proliferation...

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..We conclude that LRC are more sensitive to some proliferative stimuli than others and that changes in lineage can occur with or without recruitment of LRC into cycle...

..The mice therefore provide a useful model for non-invasive imaging of regions of high proliferation in normal or damaged epidermis...

..Our results highlight the context-dependent effects of beta1 integrin deletion and suggest that inflammation may be responsible for some of the K5Cre beta1-null phenotype...

..This work has also yielded new insights into skin tumour development...

..These findings provide a mechanistic basis for the well-established links between altered integrin expression and tumour prognosis...

..The stage is now set for exploring the relationship between the different epidermal stem cell populations and between quiescence and lineage selection...

..Growing up, some scientists enjoyed parental support, whereas for others low expectations or a geographical disadvantage were a spur to achievement. Partners can be good, bad or indifferent, but having children is not a bar to success...

..By contrast, my approach has been to focus on individual women who have 'made it' in science and to ask how their careers have been affected by their sex. Some positive conclusions emerge, but the overall picture is disheartening...

..In this review I summarize what is known about the expression and function of epidermal integrins, and highlight the challenges for future research...

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..These findings, coupled with observed dermal gene expression changes, suggest that epidermal stem cells themselves are intrinsically aging resistant and that local environmental or systemic factors modulate skin aging...

..beta1 integrins, Notch, c-Myc and beta-catenin all regulate the size of the stem cell compartment in vitro and recent evidence from transgenic mice suggests that they are also important in vivo...

..We conclude that MCSP is a novel marker for epidermal stem cells that contributes to their patterned distribution by promoting stem cell clustering...

..We conclude that interfollicular epidermis and sebaceous glands retain the ability to be reprogrammed in adult life and that continuous beta-catenin signalling is required to maintain hair follicle tumours...

..The effects on differentiation can be cell autonomous and non-autonomous, and Notch contributes to stem cell clustering via modulation of cell adhesion...

..What makes stem cell research so exciting is its tremendous potential to benefit human health and the opportunities for interdisciplinary research that it presents...

..These data suggest that suprabasal alpha6beta4 promotes tumourigenesis by preventing TGFbeta from suppressing clonal expansion of initiated cells in the epidermal basal layer...

..So, what genetic and environmental factors determine whether a mutant stem cell forms a tumour and what type of tumour will develop?..

..They also provide new insights into how integrins regulate keratinocyte differentiation...

..On transfection, all three kazrin isoforms have similar subcellular distributions. We conclude that kazrin is a novel component of desmosomes that associates with periplakin...

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..Mutant LEF1 not only inhibited expression of beta-catenin target genes but also stimulated expression of sebocyte markers, suggesting that it may determine the differentiated characteristics of sebaceous tumors...

..We describe how LRC can be visualized by whole-mount labelling of the epidermis and how purified LRC can be used to screen for markers of the epidermal stem cell compartment...

..We conclude that mutations in the beta1 I-like domain are uncommon in SCCs. However, population based studies of the polymorphisms we found may reveal an association with SCC development or prognosis...

..Recent studies challenge the existence of a transit amplifying cell compartment and suggest a new paradigm for epidermal homeostasis...

..We propose that syntenin binding to Delta1 plays a dual role in promoting intercellular adhesion and regulating Notch signalling...

..These results demonstrate that Dll1 contributes to the control of proliferation and differentiation in IFE, whereas Jagged1 regulates hair follicle differentiation...

..Thus, combined loss of the cornified envelope proteins not only impairs the epidermal barrier, but also changes the composition of T cell subpopulations in the skin...

..beta-Catenin-induced up-regulation of Jagged1 precedes induction of other Notch target genes. The different sites of expression of Hes and Hey genes suggest input from additional signaling pathways...

..We conclude that VDR is a TCF/Lef-independent transcriptional effector of the Wnt pathway and that vitamin D analogues have therapeutic potential in tumors with inappropriate activation of Wnt signalling...

..Together, our results suggest that loss of kazrinA causes defects in cell adhesion that affect axial elongation, cell differentiation, and epidermal morphogenesis...

..Our studies provide evidence for a bipotential epidermal stem cell population in an in vitro model of human epidermal lineage selection and highlight the importance of Myc as a regulator of sebocyte differentiation...

..We propose that LEF1 NH(2)-terminal mutations play a dual role in skin cancer, specifying tumor type by inhibiting Wnt signaling and acting as a tumor promoter by preventing induction of p53...

..These results suggest that down-regulation of alphavbeta5 through up-regulation of alphavbeta6 may protect SCCs from anoikis by activating an Akt survival signal...

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..These results provide a mechanism by which aberrant integrin expression triggers epidermal hyperproliferation and inflammation...

..Our data show that regulation of cell adhesion is a major function of the Myc-Miz1 complex and suggest that it may contribute to Myc-induced exit from the epidermal stem cell compartment...

..Taken together, these data suggest that the cell-surface marker MTS24 identifies a new reservoir of hair follicle keratinocytes with a proliferative capacity and gene expression profile suggestive of progenitor or stem cells...

..We also present evidence that postnatal epidermis can be reprogrammed, altering the number and location of cells that differentiate along specific epidermal lineages...

..These findings demonstrate a crucial role of beta 1 integrins in keratinocyte migration and wound re-epithelialisation. Movies available on-line..

..Because the compound affected the tumor cells at a lower concentration than primary keratinocytes, it may have potential as an antitumor therapy...

..Thus, these results indicate that ROCK plays a critical role in regulating the balance between proliferation and differentiation in human keratinocytes...

..We conclude that Nanog represses the pro-differentiation activities of NFkappaB and cooperates with Stat3 to maintain pluripotency...

..Our results show that IGF-1 and EGF can influence different components of the keratinocyte migration machinery that determines the speed of wound epithelialization...