title: Integrin-linked kinase is required for epidermal and hair follicle morphogenesis.
abstract: Integrin-linked kinase (ILK) links integrins to the actin cytoskeleton and is believed to phosphorylate several target proteins. We report that a keratinocyte-restricted deletion of the ILK gene leads to epidermal defects and hair loss. ILK-deficient epidermal keratinocytes exhibited a pronounced integrin-mediated adhesion defect leading to epidermal detachment and blister formation, disruption of the epidermal-dermal basement membrane, and the translocation of proliferating, integrin-expressing keratinocytes to suprabasal epidermal cell layers. The mutant hair follicles were capable of producing hair shaft and inner root sheath cells and contained stem cells and generated proliferating progenitor cells, which were impaired in their downward migration and hence accumulated in the outer root sheath and failed to replenish the hair matrix. In vitro studies with primary ILK-deficient keratinocytes attributed the migration defect to a reduced migration velocity and an impaired stabilization of the leading-edge lamellipodia, which compromised directional and persistent migration. We conclude that ILK plays important roles for epidermis and hair follicle morphogenesis by modulating integrin-mediated adhesion, actin reorganization, and plasma membrane dynamics in keratinocytes.
authors.affiliation: Department of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Lorenz
authors.forename: Carsten
authors.initials: C
authors.lastname: Grashoff
authors.forename: Robert
authors.initials: R
authors.lastname: Torka
authors.forename: Takao
authors.initials: T
authors.lastname: Sakai
authors.forename: Lutz
authors.initials: L
authors.lastname: Langbein
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Bloch
authors.forename: Monique
authors.initials: M
authors.lastname: Aumailley
authors.forename: Reinhard
authors.initials: R
authors.lastname: Fässler
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001485:Basement Membrane / Q000166:cytology / Q000196:embryology; D001768:Blister / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D020405:Dermis / Q000166:cytology / Q000196:embryology; D005260:Female; D018859:Hair Follicle / Q000166:cytology / Q000196:embryology*; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity / Q000235:genetics; D038081:Organogenesis / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000378:metabolism*; D011554:Pseudopodia / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D000099200:Scaffold Protein ILK
chemical_list: D000199:Actins; D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK