title: Deletion of the epidermis derived laminin γ1 chain leads to defects in the regulation of late hair morphogenesis.
abstract: Laminins are the most abundant non-collagenous basement membrane (BM) components, composed of an α, β and γ chain. The laminin γ1 chain, encoded by LAMC1, is the most abundant γ chain. The main laminin isoforms in the dermo-epidermal junction (DEJ) are laminin-332, laminin-511 and laminin-211, the latter being restricted to the lower part of hair follicles (HFs). Complete deletion of LAMC1 results in lethality around embryonic day 5.5. To study the function of laminin γ1 containing isoforms in skin development and maturation after birth, we generated mice lacking LAMC1 expression in basal keratinocytes (LAMC1EKO) using the keratin 14 (K14) Cre/loxP system. This deletion resulted in loss of keratinocyte derived laminin-511 and in deposition of fibroblast derived laminin-211 throughout the whole DEJ. The DEJ in areas between hemidesmosomes was thickened, whereas hemidesmosome morphology was normal. Most strikingly, LAMC1EKOmice showed delayed HF morphogenesis accompanied by reduced proliferation of hair matrix cells and impaired differentiation of hair shafts (HS). However, this deletion did not interfere with early HF development, since placode numbers and embryonic hair germ formation were not affected. Microarray analysis of skin revealed down regulation of mainly different hair keratins. This is due to reduced expression of transcription factors such as HoxC13, FoxN1, FoxQ1 and Msx2, known to regulate expression of hair keratins. While the role of laminin-511 in signaling during early hair germ formation and elongation phase has been described, we here demonstrate that epidermal laminin-511 is also a key regulator for later hair development and HS differentiation.
authors.affiliation: Dermatology, University of Cologne, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Fleger-Weckmann
authors.affiliation: Dermatology, University of Cologne, Germany.
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Üstün
authors.affiliation: Dermatology, University of Lübeck, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kloepper
authors.affiliation: Dermatology, University of Manchester, UK.
authors.forename: Ralf
authors.initials: R
authors.lastname: Paus
authors.affiliation: German Sport University Cologne, Germany.
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Bloch
authors.affiliation: Neurobiology and Genetics, Rockefeller University, New York, USA.
authors.forename: Zu-Lin
authors.initials: ZL
authors.lastname: Chen
authors.affiliation: Physiological Chemistry and Pathobiochemistry, University of Muenster, Germany; Cells-in-Motion Cluster of Excellence, University of Muenster, Germany.
authors.forename: Jeannine
authors.initials: J
authors.lastname: Wegner
authors.affiliation: Physiological Chemistry and Pathobiochemistry, University of Muenster, Germany; Cells-in-Motion Cluster of Excellence, University of Muenster, Germany.
authors.forename: Lydia
authors.initials: L
authors.lastname: Sorokin
authors.affiliation: German Cancer Research Center, Heidelberg, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Langbein
authors.affiliation: Dermatology, University of Cologne, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Eckes
authors.affiliation: Dermatology, University of Cologne, Germany.
authors.forename: Paola
authors.initials: P
authors.lastname: Zigrino
authors.affiliation: Dermatology, University of Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Germany. Electronic address: thomas.krieg@uni-koeln.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Krieg
authors.affiliation: Dermatology, University of Cologne, Germany.
authors.forename: Roswitha
authors.initials: R
authors.lastname: Nischt
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D017353:Gene Deletion; D015870:Gene Expression; D018859:Hair Follicle / Q000166:cytology / Q000196:embryology / Q000254:growth & development*; D015603:Keratinocytes / Q000378:metabolism; D007797:Laminin / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009024:Morphogenesis
chemical_list: D007797:Laminin; C089141:laminin gamma 1
keywords: Basement membrane; Hair follicle; Laminin-211; Laminin-511; Skin