Essential role of polarity protein Par3 for epidermal homeostasis through regulation of barrier function, keratinocyte differentiation and stem cell maintenance

Ali NJ, Dias Gomes M, Bauer R, Brodesser S, Niemann C, Iden S

J. Invest. Dermatol. 2016 Jul;

PMID: 27452221


Partitioning-defective (Par) proteins contribute to multiprotein complexes that drive cell polarity and fate in invertebrates. Of these, the ternary Par3-aPKC-Par6 polarity complex mediates asymmetry in various systems, whereas Par3 and aPKC/Par6 can also act independently. aPKCλ 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, while 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 aPKCλ 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 following Par3 inactivation is unlikely to be attributed to increased perpendicular spindle orientation. Collectively, mammalian Par3 controls epidermal barrier, differentiation and stem cell maintenance in the pilosebaceous unit, which are all essential for the homeostasis of an important barrier-forming epithelium.

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