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SVEP 1 plays a crucial role in epidermal differentiation
Author(s) -
Samuelov Liat,
Li Qiaoli,
Bochner Ron,
Najor Nicole A.,
Albrecht Lauren,
Malchin Natalia,
Goldsmith Tomer,
GrafiCohen Meital,
Vodo Dan,
Fainberg Gilad,
Meilik Benjamin,
Goldberg Ilan,
Warshauer Emily,
Rogers Tova,
Edie Sarah,
IshidaYamamoto Akemi,
Burzenski Lisa,
Erez Noam,
Murray Steve A.,
Irvine Alan D.,
Shultz Lenny,
Green Kathleen J.,
Uitto Jouni,
Sprecher Eli,
Sarig Ofer
Publication year - 2017
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.13256
Subject(s) - epidermis (zoology) , keratinocyte , microbiology and biotechnology , biology , downregulation and upregulation , cell culture , anatomy , genetics , gene
Abstract SVEP 1 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 SVEP 1 function in the epidermis. SVEP 1 was found by qRT ‐ PCR to be ubiquitously expressed in human tissues, including the skin. Confocal microscopy revealed that SVEP 1 is normally mostly expressed in the cytoplasm of basal and suprabasal epidermal cells. Downregulation of SVEP 1 expression in primary keratinocytes resulted in decreased expression of major epidermal differentiation markers. Similarly, SVEP 1 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 SVEP 1. Homozygous Svep1 knockout mice were embryonic lethal. Thus, to assess the importance of SVEP 1 for normal skin homoeostasis in vivo, we downregulated SVEP 1 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 SVEP 1 plays a critical role during epidermal differentiation.