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

The transcription factor, NF- κB, is required for normal development of epidermal appendages, including hair follicles, teeth, and exocrine glands. However, little was known about the precise functional role of NF-κB and its integration into developmental signaling cascades. Now, Ruth Schmidt-Ullrich and colleagues (laboratory of Professor Claus Scheidereit) report that during placode formation of guard hairs (one of four murine pelage hair types), NF- κB controls the transition from the initially non-proliferative to the proliferative stage (Development 2006 133:1045-1057). Mice with suppressed NF- κB activity (c ^{IκB αΔ N} ), inactive ectodysplasin A1 (Eda A1; tabby mice), or Eda A1 receptor (EdaR; downless mice) share identical hair defects. Crossing tabby and downless mice with NF- κB reporter mice revealed that Eda A1/EdaR signalling activates NF- κB, which then triggers placode cell proliferation by inducing sonic hedgehog and cyclin D1 expression. While Wnt signalling is needed for initiation of placode formation, downstream Eda A1/EdaR/NF-κB is essential for the down growth of guard hair placodes into the underlying mesoderm, eventually giving rise to a hair follicle. Eda A1, EdaR, and NF- κB also control the morphology of other hair types, where additional signals modulate NF- κB activity. In addition to providing insights into the molecular mechanisms of NF- κB action during embryonic development, this newly revealed link to growth promoting cascades may give further clues to the role of NF- κB in tumor biology .

Contact:

Pamela Cohen
p.cohen@mdc-berlin.de
+49 30 9406 2121