Activation of the Notch pathway in the hair cortex leads to aberrant differentiation of the adjacent hair-shaft layers

Little is known about the mechanisms underlying the generation of various c ell types in the hair follicle. To investigate the role of the Notch pathwa y in this process, transgenic mice were generated in which an active form o f Notch1 (Notch(Delta E)) was overexpressed under the control of the mouse hair keratin A1 (MHKA1) promoter, MHKA-Notch(Delta E) is expressed only in one precursor cell type of the hair follicle, the cortex. Transgenic mice c ould be easily identified by the phenotypes of curly whiskers and wavy, she en pelage hair. No effects of activated Notch on proliferation were detecte d in hair follicles of the transgenic mice. We find that activating Notch s ignaling in the cortex caused abnormal differentiation of the medulla and t he cuticle, two neighboring cell types that did not express activated Notch . We demonstrate that these nonautonomous effects are likely caused by cell -cell interactions between keratinocytes within the hair follicle and that Notch may function in such interactions either by directing the differentia tion of follicular cells or assisting cells in interpreting a gradient eman ating from the dermal papilla.