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 [1-9]. Notch interaction with its ligand induces the cleavage of its intracellular domain (IC) [10], and the Notch IC translocates to the nucleus and binds to RBP-J [11] to transactivate transcription of target genes [10, 12]. All four Notches in mammals [13-17] bind to RBP-J to exert their transactivation activities. Notch is expressed in developing or differentiating epidermis and hairs [13-15, 18-20], inhibits the terminal differentiation of the epidermis [21], and regulates hair differentiation [22]. The common stem cells that reside in the upper portion of hair follicles (the bulge) contribute to epidermal and hair cell formation [23, 24]. 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 [25] 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.