Universität zu Köln

Ali, Noelle J. A., Gomes, Martim Dias, Bauer, Ronja, Brodesser, Susanne, Niemann, Catherin and Iden, Sandra ORCID: 0000-0003-2333-9827 (2016). Essential Role of Polarity Protein Par3 for Epidermal Homeostasis through Regulation of Barrier Function, Keratinocyte Differentiation, and Stem Cell Maintenance. J. Invest. Dermatol., 136 (12). S. 2406 - 2417. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1523-1747

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Abstract

Partitioning-defective (Par) proteins contribute to multiprotein complexes that drive cell polarity and fate in invertebrates. Of these, the ternary Par3-atypical protein kinase C-Par6 polarity complex mediates asymmetry in various systems, whereas Par3 and aPKC/Par6 can also act independently. aPKC-lambda has recently been implicated in epidermal differentiation and stem cell fate; however, whether Par3 contributes to the homeostasis of adult stratified epithelia is currently unknown. Here, we provide functional evidence that epidermal Par3 loss disturbed the inside-out skin barrier, coinciding with altered expression and localization of principle tight junction components, and that epidermal differentiation and thickness were increased. Moreover, Par3 inactivation caused an initial expansion and later decline of hair follicle bulge stem cells, accompanied by an enrichment of committed progenitors, formation of hypertrophic sebaceous glands, and increased epidermal differentiation, suggesting aberrant cell fate decisions. Importantly, and opposite to aPKC lambda deletion, Par3 loss did not enhance perpendicular cell divisions. Instead, in Par3-deficient hair follicles, spindles were shifted toward planar orientation, indicating that abnormal differentiation after Par3 inactivation is unlikely to be attributed to increased perpendicular spindle orientation. Collectively, mammalian Par3 controls the epidermal barrier, differentiation, and stem cell maintenance in the pilosebaceous unit, which are all essential for the homeostasis of an important barrier-forming epithelium.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Ali, Noelle J. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gomes, Martim Dias UNSPECIFIED UNSPECIFIED UNSPECIFIED Bauer, Ronja UNSPECIFIED UNSPECIFIED UNSPECIFIED Brodesser, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Niemann, Catherin UNSPECIFIED UNSPECIFIED UNSPECIFIED Iden, Sandra UNSPECIFIED orcid.org/0000-0003-2333-9827 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-254435
DOI:	10.1016/j.jid.2016.07.011
Journal or Publication Title:	J. Invest. Dermatol.
Volume:	136
Number:	12
Page Range:	S. 2406 - 2417
Date:	2016
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1523-1747
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HAIR FOLLICLE MORPHOGENESIS; TIGHT JUNCTION FORMATION; ADHESION MOLECULE JAM; SEBACEOUS GLAND; DIVISION; COMPLEX; NICHE; EPITHELIA; SKIN; IDENTIFICATION Multiple languages Dermatology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/25443