Abstract
A novel function of NF- Kappa B in the development of most ectodermal appendages, including two types of murine pelage hair follicles, was detected in a mouse model with suppressed NF- Kappa B activity (c super(I Kappa B alpha Delta N)). However, the developmental processes regulated by NF- Kappa B in hair follicles has remained unknown. Furthermore, the similarity between the phenotypes of c super(I Kappa BA Delta N) mice and mice deficient in Eda A1 (tabby) or its receptor EdaR (downless) raised the issue of whether in vivo NF- Kappa B regulates or is regulated by these novel TNF family members. We now demonstrate that epidermal NF- Kappa B activity is first observed in placodes of primary guard hair follicles at day E14.5, and that in vivo NF- Kappa B signalling is activated downstream of Eda A1 and EdaR. Importantly, ectopic signals which activate NF- Kappa B can also stimulate guard hair placode formation, suggesting a crucial role for NF- Kappa B in placode development. In downless and c super(I Kappa B alpha Delta N) mice, placodes start to develop, but rapidly abort in the absence of EdaR/NF- Kappa B signalling. We show that NF- Kappa B 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- Kappa B, probably via Shh and Wnt. The strongly decreased number of hair follicles observed in c super(I Kappa B alpha Delta N) mice compared with tabby mice, indicates that additional signals, such as TROY, must regulate NF- Kappa B activity in specific hair follicle subtypes.
