title: Activation of the Notch pathway in the hair cortex leads to aberrant differentiation of the adjacent hair-shaft layers.
abstract: Little is known about the mechanisms underlying the generation of various cell types in the hair follicle. To investigate the role of the Notch pathway in this process, transgenic mice were generated in which an active form of Notch1 (Notch(DeltaE)) was overexpressed under the control of the mouse hair keratin A1 (MHKA1) promoter. MHKA-Notch(DeltaE) is expressed only in one precursor cell type of the hair follicle, the cortex. Transgenic mice could be easily identified by the phenotypes of curly whiskers and wavy, sheen pelage hair. No effects of activated Notch on proliferation were detected in hair follicles of the transgenic mice. We find that activating Notch signaling in the cortex caused abnormal differentiation of the medulla and the cuticle, two neighboring cell types that did not express activated Notch. We demonstrate that these non-autonomous 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 differentiation of follicular cells or assisting cells in interpreting a gradient emanating from the dermal papilla.
authors.affiliation: Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, MO 63110, USA.
authors.forename: M H
authors.initials: MH
authors.lastname: Lin
authors.forename: C
authors.initials: C
authors.lastname: Leimeister
authors.forename: M
authors.initials: M
authors.lastname: Gessler
authors.forename: R
authors.initials: R
authors.lastname: Kopan
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D006197:Hair / Q000002:abnormalities; D006201:Hair Diseases; D018859:Hair Follicle / Q000002:abnormalities* / Q000378:metabolism*; D007633:Keratins / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D014157:Transcription Factors
chemical_list: D008565:Membrane Proteins; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D007633:Keratins