SVEP1 plays a crucial role in epidermal differentiation.
Document Type
Article
Publication Date
5-2017
JAX Source
Exp Dermatol 2017 May; 26(5):423-430
Volume
26
Issue
5
First Page
423
Last Page
430
ISSN
1600-0625
PMID
27892606
DOI
https://doi.org/10.1111/exd.13256
Grant
AR043380, AR041836, CA122151
Abstract
SVEP1 is a recently identified multidomain cell adhesion protein, homologous to the mouse polydom protein, which has been shown to mediate cell-cell adhesion in an integrin-dependent manner in osteogenic cells. In this study, we characterized SVEP1 function in the epidermis. SVEP1 was found by qRT-PCR to be ubiquitously expressed in human tissues, including the skin. Confocal microscopy revealed that SVEP1 is normally mostly expressed in the cytoplasm of basal and suprabasal epidermal cells. Downregulation of SVEP1 expression in primary keratinocytes resulted in decreased expression of major epidermal differentiation markers. Similarly, SVEP1 downregulation was associated with disturbed differentiation and marked epidermal acanthosis in three-dimensional skin equivalents. In contrast, the dispase assay failed to demonstrate significant differences in adhesion between keratinocytes expressing normal vs low levels of SVEP1. Homozygous Svep1 knockout mice were embryonic lethal. Thus, to assess the importance of SVEP1 for normal skin homoeostasis in vivo, we downregulated SVEP1 in zebrafish embryos with a Svep1-specific splice morpholino. Scanning electron microscopy revealed a rugged epidermis with perturbed microridge formation in the centre of the keratinocytes of morphant larvae. Transmission electron microscopy analysis demonstrated abnormal epidermal cell-cell adhesion with disadhesion between cells in Svep1-deficient morphant larvae compared to controls. In summary, our results indicate that SVEP1 plays a critical role during epidermal differentiation. Exp Dermatol 2017 May; 26(5):423-430.
Recommended Citation
Samuelov L,
Li Q,
Bochner R,
Najor N,
Albrecht L,
Malchin N,
Goldsmith T,
Grafi-Cohen M,
Vodo D,
Fainberg G,
Meilik B,
Goldberg I,
Warshauer E,
Rogers T,
Edie S,
Ishida-Yamamoto A,
Burzenski LM,
Erez N,
Murray S,
Irvine A,
Shultz LD,
Green K,
Uitto J,
Sprecher E,
Sarig O.
SVEP1 plays a crucial role in epidermal differentiation. Exp Dermatol 2017 May; 26(5):423-430