title: SVEP1 plays a crucial role in epidermal differentiation.
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.
authors.affiliation: Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Liat
authors.initials: L
authors.lastname: Samuelov
authors.affiliation: Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Qiaoli
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Ron
authors.initials: R
authors.lastname: Bochner
authors.affiliation: Departments of Pathology and Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Najor
authors.affiliation: Departments of Pathology and Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Albrecht
authors.affiliation: Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Natalia
authors.initials: N
authors.lastname: Malchin
authors.affiliation: Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Tomer
authors.initials: T
authors.lastname: Goldsmith
authors.affiliation: Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Meital
authors.initials: M
authors.lastname: Grafi-Cohen
authors.affiliation: Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Dan
authors.initials: D
authors.lastname: Vodo
authors.affiliation: Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Gilad
authors.initials: G
authors.lastname: Fainberg
authors.affiliation: Department of Plastic and Reconstructive Surgery, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Meilik
authors.affiliation: Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Ilan
authors.initials: I
authors.lastname: Goldberg
authors.affiliation: Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Emily
authors.initials: E
authors.lastname: Warshauer
authors.affiliation: Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Tova
authors.initials: T
authors.lastname: Rogers
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Edie
authors.affiliation: Department of Dermatology, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Akemi
authors.initials: A
authors.lastname: Ishida-Yamamoto
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Burzenski
authors.affiliation: The Research Center for Digestive Tract and Liver Diseases, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Noam
authors.initials: N
authors.lastname: Erez
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME, USA.
authors.forename: Steve A
authors.initials: SA
authors.lastname: Murray
authors.affiliation: Department of Clinical Medicine, Trinity College, Dublin, Ireland.
authors.forename: Alan D
authors.initials: AD
authors.lastname: Irvine
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME, USA.
authors.forename: Lenny
authors.initials: L
authors.lastname: Shultz
authors.affiliation: Departments of Pathology and Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Kathleen J
authors.initials: KJ
authors.lastname: Green
authors.affiliation: Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Jouni
authors.initials: J
authors.lastname: Uitto
authors.affiliation: Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.|Department of Human Molecular Genetics & Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.
authors.forename: Eli
authors.initials: E
authors.lastname: Sprecher
authors.affiliation: Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Sarig
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002454:Cell Differentiation; D004817:Epidermis / Q000378:metabolism* / Q000648:ultrastructure*; D015870:Gene Expression; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D018345:Mice, Knockout; D061251:Primary Cell Culture; D015027:Zebrafish
chemical_list: D015815:Cell Adhesion Molecules; C508516:SVEP1 protein, human
keywords: SVEP1; epidermal differentiation; integrin α9β1; zebrafish