Notch/RBP-J Signaling Regulates Epidermis/Hair Fate Determination of Hair Follicular Stem Cells

Notch signaling is involved in the cell fate determination of various cell lineages. Notch interaction with its ligand induces the cleavage of its intracellular domain (IC), and the Notch IC translocates to the nucleus and binds to RBP-J to transactivate transcription of target genes. All four Notches in mammals bind to RBP-J to exert their transactivation activities. Notch is expressed in developing or differentiating epidermis and hairs, inhibits the terminal differentiation of the epidermis, and regulates hair differentiation. The common stem cells that reside in the upper portion of hair follicles (the bulge) contribute to epidermal and hair cell formation. However, it is unknown what determines whether hair follicular stem cells will become hairs or epidermis. Here we report that conditionally disrupting the mouse RBP-J gene in a mosaic pattern to avoid embryonic lethality of RBP-J-deficiency caused hair loss, epidermal hyperkeratinization, and epidermal cyst formation. Cyst formation is probably due to a combination of the aberrant fate determination of RBP-J-deficient stem cells to epidermal progenitors and their accelerated differentiation into epidermis. These results suggest that Notch/RBP-J signaling regulates the cell fate determination of hair follicular stem cells at the bulge region.