title: Heparan sulfate regulates hair follicle and sebaceous gland morphogenesis and homeostasis.
abstract: Hair follicle (HF) morphogenesis and cycling are a result of intricate autonomous epithelial-mesenchymal interactions. Once the first HF cycle is complete it repeatedly undergoes cyclic transformations. Heparan sulfate (HS) proteoglycans are found on the cell surface and in the extracellular matrix where they influence a variety of biological processes by interacting with physiologically important proteins, such as growth factors. Inhibition of heparanase (an HS endoglycosidase) in in vitro cultured HFs has been shown to induce a catagen-like process. Therefore, this study aimed to elucidate the precise role of HS in HF morphogenesis and cycling. An inducible tetratransgenic mouse model was generated to excise exostosin glycosyltransferase 1 (Ext1) in keratin 14-positive cells from P21. Interestingly, EXT1(StEpiΔ/StEpiΔ) mice presented solely anagen HFs. Moreover, waxing the fur to synchronize the HFs revealed accelerated hair regrowth in the EXT1(StEpiΔ/StEpiΔ) mice and hindered cycling into catagen. The ablation of HS in the interfollicular epidermal cells of mature skin led to the spontaneous formation of new HFs and an increase in Sonic Hedgehog expression resembling wild-type mice at P0, thereby indicating that the HS/Sonic Hedgehog signaling pathway regulates HF formation during embryogenesis and prevents HF formation in mature skin. Finally, the knock-out of HS also led to the morphogenesis and hyperplasia of sebaceous glands and sweat glands in mature mice, leading to exacerbated sebum production and accumulation on the skin surface. Therefore, our findings clearly show that an intricate control of HS levels is required for HF, sebaceous gland, and sweat gland morphogenesis and HF cycling.
authors: From the Department of Ophthalmology, University of Cincinnati, Cincinnati, Ohio 45267-0838, vcoulsonthomas@gmail.com vc315@cam.ac.uk.
authors: Vivien Jane
authors: VJ
authors: Coulson-Thomas
authors: From the Department of Ophthalmology, University of Cincinnati, Cincinnati, Ohio 45267-0838, Division of Developmental Biology, Cincinnati Children's Hospital and Research, Cincinnati, Ohio 45229-3039, and.
authors: Tarsis Ferreira
authors: TF
authors: Gesteira
authors: Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, California 92093-0687.
authors: Jeffrey
authors: J
authors: Esko
authors: From the Department of Ophthalmology, University of Cincinnati, Cincinnati, Ohio 45267-0838.
authors: Winston
authors: W
authors: Kao
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D053331:Ectodysplasins / Q000378:metabolism; D018859:Hair Follicle / Q000254:growth & development / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006497:Heparan Sulfate / Q000378:metabolism*; D006706:Homeostasis; D007150:Immunohistochemistry; D053547:Keratin-14 / Q000378:metabolism; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009024:Morphogenesis; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism; D012627:Sebaceous Glands / Q000254:growth & development / Q000378:metabolism*; D015398:Signal Transduction; D012867:Skin / Q000254:growth & development / Q000378:metabolism; D053667:Syndecans / Q000378:metabolism; D051155:Wnt1 Protein / Q000378:metabolism; D000099058:Exostosin 1
chemical_list: D053331:Ectodysplasins; D053823:Hedgehog Proteins; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D053547:Keratin-14; D017351:N-Acetylglucosaminyltransferases; D053667:Syndecans; D051155:Wnt1 Protein; D000099058:Exostosin 1; C506019:Eda protein, mouse; C465570:Shh protein, mouse; C495246:Wnt1 protein, mouse; C071927:perlecan
keywords: Development; Glycosaminoglycan; Hair Follicle; Heparan Sulfate; Proteoglycan; Sebaceous Gland; Skin; Syndecan 1; Syndecan 3