SVEP1 plays a crucial role in epidermal differentiation

Liat Samuelov, Qiaoli Li, Ron Bochner, Nicole A. Najor, Lauren Albrecht, Natalia Malchin, Tomer Goldsmith, Meital Grafi-Cohen, Dan Vodo, Gilad Fainberg, Benjamin Meilik, Ilan Goldberg, Emily Warshauer, Tova Rogers, Sarah Edie, Akemi Ishida-Yamamoto, Lisa Burzenski, Noam Erez, Steve A. Murray, Alan D. IrvineLenny Shultz, Kathleen J. Green, Jouni Uitto, Eli Sprecher*, Ofer Sarig

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)423-430
Number of pages8
JournalExperimental Dermatology
Volume26
Issue number5
DOIs
StatePublished - May 2017

Keywords

  • SVEP1
  • epidermal differentiation
  • integrin α9β1
  • zebrafish

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

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