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In this study, we characterized <jats:styled-content style=\"fixed-case\">SVEP<\/jats:styled-content>1 function in the epidermis. <jats:italic><jats:styled-content style=\"fixed-case\">SVEP<\/jats:styled-content>1<\/jats:italic> was found by <jats:styled-content style=\"fixed-case\">qRT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> to be ubiquitously expressed in human tissues, including the skin. Confocal microscopy revealed that <jats:styled-content style=\"fixed-case\">SVEP<\/jats:styled-content>1 is normally mostly expressed in the cytoplasm of basal and suprabasal epidermal cells. Downregulation of <jats:italic><jats:styled-content style=\"fixed-case\">SVEP<\/jats:styled-content>1<\/jats:italic> expression in primary keratinocytes resulted in decreased expression of major epidermal differentiation markers. Similarly, <jats:italic><jats:styled-content style=\"fixed-case\">SVEP<\/jats:styled-content>1<\/jats:italic> downregulation was associated with disturbed differentiation and marked epidermal acanthosis in three\u2010dimensional skin equivalents. In contrast, the dispase assay failed to demonstrate significant differences in adhesion between keratinocytes expressing normal vs low levels of <jats:styled-content style=\"fixed-case\">SVEP<\/jats:styled-content>1. Homozygous Svep1 knockout mice were embryonic lethal. Thus, to assess the importance of <jats:styled-content style=\"fixed-case\">SVEP<\/jats:styled-content>1 for normal skin homoeostasis in vivo, we downregulated <jats:italic><jats:styled-content style=\"fixed-case\">SVEP<\/jats:styled-content>1<\/jats:italic> in zebrafish embryos with a <jats:italic>Svep1<\/jats:italic>\u2010specific 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\u2010cell adhesion with disadhesion between cells in <jats:italic>Svep1<\/jats:italic>\u2010deficient morphant larvae compared to controls. In summary, our results indicate that <jats:styled-content style=\"fixed-case\">SVEP<\/jats:styled-content>1 plays a critical role during epidermal differentiation.<\/jats:p>","DOI":"10.1111\/exd.13256","type":"journal-article","created":{"date-parts":[[2016,11,28]],"date-time":"2016-11-28T12:36:47Z","timestamp":1480336607000},"page":"423-430","source":"Crossref","is-referenced-by-count":39,"title":["<scp>SVEP<\/scp>1 plays a crucial role in epidermal differentiation"],"prefix":"10.1111","volume":"26","author":[{"given":"Liat","family":"Samuelov","sequence":"first","affiliation":[{"name":"Department of Dermatology Tel Aviv Sourasky Medical Center  Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoli","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Cutaneous Biology Sidney Kimmel Medical College Thomas Jefferson University  Philadelphia PA 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