Universität zu Köln

Fleger-Weckmann, Anja, Uestuen, Yasemin, Kloepper, Jennifer, Paus, Ralf, Bloch, Wilhelm, Chen, Zu-Lin, Wegner, Jeannine, Sorokin, Lydia, Langbein, Lutz, Eckes, Beate, Zigrino, Paola ORCID: 0000-0002-7470-0064, Krieg, Thomas and Nischt, Roswitha (2016). Deletion of the epidermis derived laminin gamma 1 chain leads to defects in the regulation of late hair morphogenesis. Matrix Biol., 56. S. 42 - 57. AMSTERDAM: ELSEVIER SCIENCE BV. ISSN 1569-1802

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Abstract

Laminins are the most abundant non-collagenous basement membrane (BM) components, composed of an a, beta and gamma chain. The laminin gamma 1 chain, encoded by LAMC1, is the most abundant gamma 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 gamma 1 containing isoforms in skin development and maturation after birth, we generated mice lacking LAMC1 expression in basal keratinocytes (LAMC1(EKO) 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, LAMC1(EKO) mice 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. (C) 2016 Elsevier B.V. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Fleger-Weckmann, Anja UNSPECIFIED UNSPECIFIED UNSPECIFIED Uestuen, Yasemin UNSPECIFIED UNSPECIFIED UNSPECIFIED Kloepper, Jennifer UNSPECIFIED UNSPECIFIED UNSPECIFIED Paus, Ralf UNSPECIFIED UNSPECIFIED UNSPECIFIED Bloch, Wilhelm UNSPECIFIED UNSPECIFIED UNSPECIFIED Chen, Zu-Lin UNSPECIFIED UNSPECIFIED UNSPECIFIED Wegner, Jeannine UNSPECIFIED UNSPECIFIED UNSPECIFIED Sorokin, Lydia UNSPECIFIED UNSPECIFIED UNSPECIFIED Langbein, Lutz UNSPECIFIED UNSPECIFIED UNSPECIFIED Eckes, Beate UNSPECIFIED UNSPECIFIED UNSPECIFIED Zigrino, Paola UNSPECIFIED orcid.org/0000-0002-7470-0064 UNSPECIFIED Krieg, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Nischt, Roswitha UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-254941
DOI:	10.1016/j.matbio.2016.05.002
Journal or Publication Title:	Matrix Biol.
Volume:	56
Page Range:	S. 42 - 57
Date:	2016
Publisher:	ELSEVIER SCIENCE BV
Place of Publication:	AMSTERDAM
ISSN:	1569-1802
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BASEMENT-MEMBRANE PROTEINS; EXTRACELLULAR-MATRIX; FOLLICLE DEVELOPMENT; ALPHA-DYSTROGLYCAN; CELL-ADHESION; STEM-CELLS; EXPRESSION; BINDING; SKIN; GENE Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/25494