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    NF-kappaB transmits Eda A1/EdaR signalling to activate Shh and cyclin D1 expression, and controls post-initiation hair placode down growth.

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    Publication date
    2000
    Author
    Schmidt-Ullrich, R.
    Tobin, Desmond J.
    Lenhard, D.
    Schneider, P
    Paus, R.
    Scheidereit, C.
    Keyword
    TNF
    Hair follicle
    NF-KB
    Eda A1
    EdaR
    Skin
    Mouse
    TROY (Tnfrsf19)
    Cyclin D1
    Peer-Reviewed
    Yes
    
    Metadata
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    Abstract
    A novel function of NF-KB in the development of most ectodermal appendages, including two types of murine pelage hair follicles, was detected in a mouse model with suppressed NF-KB activity (CI¿B¿¿N). However, the developmental processes regulated by NF-¿B in hair follicles has remained unknown. Furthermore, the similarity between the phenotypes of CI¿BA¿N mice and mice deficient in Eda A1 (tabby) or its receptor EdaR (downless) raised the issue of whether in vivo NF-KB regulates or is regulated by these novel TNF family members. We now demonstrate that epidermal NF-KB activity is first observed in placodes of primary guard hair follicles at day E14.5, and that in vivo NF-KB signalling is activated downstream of Eda A1 and EdaR. Importantly, ectopic signals which activate NF-KB can also stimulate guard hair placode formation, suggesting a crucial role for NF-KB in placode development. In downless and CI¿B¿¿N mice, placodes start to develop, but rapidly abort in the absence of EdaR/NF-KB signalling. We show that NF-KB activation is essential for induction of Shh and cyclin D1 expression and subsequent placode down growth. However, cyclin D1 induction appears to be indirectly regulated by NF-KB, probably via Shh and Wnt. The strongly decreased number of hair follicles observed in CI¿B¿¿N mice compared with tabby mice, indicates that additional signals, such as TROY, must regulate NF-KB activity in specific hair follicle subtypes.
    URI
    http://hdl.handle.net/10454/3870
    Version
    No full-text available in the repository
    Citation
    Schmidt-Ullrich, R., Tobin, D.J., Lenhara, D. and Schneider, P. et al. (2000). NF-kappaB transmits Eda A1/EdaR signalling to activate Shh and cyclin D1 expression, and controls post-initiation hair placode down growth. Development. Vol. 133, No. 6, pp. 1045-1057.
    Link to publisher’s version
    http://dx.doi.org/10.1242/dev.02278
    Type
    Article
    Collections
    Life Sciences Publications

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