α-parvin is required for epidermal morphogenesis, hair follicle development and basal keratinocyte polarity.

Johannes Altstätter,Michael W Hess,Mercedes Costell,Eloi Montanez,Erik H J Danen

doi:10.1371/journal.pone.0230380

Johannes Altstätter, Michael W Hess + Show 3 more

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https://doi.org/10.1371/journal.pone.0230380

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Abstract

Epidermal morphogenesis and hair follicle (HF) development depend on the ability of keratinocytes to adhere to the basement membrane (BM) and migrate along the extracellular matrix. Integrins are cell-matrix receptors that control keratinocyte adhesion and migration, and are recognized as major regulators of epidermal homeostasis. How integrins regulate the behavior of keratinocytes during epidermal morphogenesis remains insufficiently understood. Here, we show that α-parvin (α-pv), a focal adhesion protein that couples integrins to actin cytoskeleton, is indispensable for epidermal morphogenesis and HF development. Inactivation of the murine α-pv gene in basal keratinocytes results in keratinocyte-BM detachment, epidermal thickening, ectopic keratinocyte proliferation and altered actin cytoskeleton polarization. In vitro, α-pv-null keratinocytes display reduced adhesion to BM matrix components, aberrant spreading and stress fibers formation, and impaired directed migration. Together, our data demonstrate that α-pv controls epidermal homeostasis by facilitating integrin-mediated adhesion and actin cytoskeleton organization in keratinocytes.

Highlights

The epidermis of vertebrates is a stratified squamous epithelium, consisting of multiple layers of keratinocytes that are separated from the underlying dermis by the basement membrane (BM), a specialized extracellular matrix (ECM) rich in laminins and collagens [1]
Deletion of the α-pv gene in keratinocytes in mice has three main consequences: 1) keratinocyte-BM detachment resulting in subepidermal blisters and distorted BM organization, 2) impaired hair follicle (HF) development and maintenance causing progressive and persistent alopecia, and 3) impaired epidermal differentiation manifested as epidermal hyperproliferation and thickening, and abnormal expression of epidermal differentiation makers
Adhesion of basal keratinocytes to the BM is mainly mediated by α6β4 and α3β1 integrins, which bind to LN-332, the main matrix component of the BM [5, 8]

Summary

Introduction

The epidermis of vertebrates is a stratified squamous epithelium, consisting of multiple layers of keratinocytes that are separated from the underlying dermis by the basement membrane (BM), a specialized extracellular matrix (ECM) rich in laminins and collagens [1]. Once basal keratinocytes commit to a terminal differentiation program, they exit the cell cycle, detach from the BM and migrate upwards through the suprabasal layers. This cell transition is accompanied by the successive differentiation of basal keratinocytes into terminally differentiated corneocytes, which will eventually be shaded from the outer layer as dead squames [2]. Loss of basal keratinocytes is replenished by stem cells that reside in the basal layer of the epidermis, in the sebaceous glands and in the bulge of hair follicles (HFs) [3].

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