2001
DOI: 10.1038/ncb1201-1076
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Desmoplakin is essential in epidermal sheet formation

Abstract: We have generated an epidermis-specific desmoplakin (DP) mouse knockout, and show that epidermal integrity requires DP; mechanical stresses to DP-null skin cause intercellular separations. The number of epidermal desmosomes in DP-null skin is similar to wild type (WT), but they lack keratin filaments, which compromise their function. DP-null keratinocytes have few desmosomes in vitro, and are unable to undergo actin reorganization and membrane sealing during epithelial sheet formation. Adherens junctions are a… Show more

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Cited by 277 publications
(344 citation statements)
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“…DSP KO embryos did not survive beyond embryonic day 6.5 and displayed severe defects in tissue architecture, shaping of the embryo, and in anchoring keratin filaments to desmosomes (Gallicano et al 1998). In an epidermisspecific DSP KO, intercellular separations were observed as expected (Vasioukhin et al 2001). Surprisingly, desmosome number was unaltered although the lack of keratin association compromised their function.…”
Section: Evidence From Mouse Models and Human Diseasesmentioning
confidence: 91%
See 1 more Smart Citation
“…DSP KO embryos did not survive beyond embryonic day 6.5 and displayed severe defects in tissue architecture, shaping of the embryo, and in anchoring keratin filaments to desmosomes (Gallicano et al 1998). In an epidermisspecific DSP KO, intercellular separations were observed as expected (Vasioukhin et al 2001). Surprisingly, desmosome number was unaltered although the lack of keratin association compromised their function.…”
Section: Evidence From Mouse Models and Human Diseasesmentioning
confidence: 91%
“…Desmosomes have been recognized early on as important sites for KIF formation and organization in vivo (Jackson et al 1980;Bologna et al 1986;Schwarz et al 2015), and genetic deletion of DSP can cause extensive reorganization or collapse of KIF, depending on the cell type (Gallicano et al 1998;Vasioukhin et al 2001;Sumigray and Lechler 2012). Moreover, DSP and DSG1 mutations can give rise to SPPK (OMIM #612908, #148700, respectively), a hyperkeratotic skin condition with fewer or smaller desmosomes in the suprabasal epidermis and perinuclear accumulation of KIF in DSP-associated SPPK (Wan et al 2004).…”
Section: Interdependence Of Keratins and Desmosomesmentioning
confidence: 99%
“…Conditional ablation of desmoplakin in the mouse epidermis reveals a role of the protein in formation and maintenance of epithelial sheets (Vasioukhin et al, 2001). Disassembly of desmosomes at the onset of cytokine-induced EMT is regulated by Slug, a zinc-finger transcriptional repressor that inhibits the desmoplakin and desmoglein genes to facilitate progression of EMT (Savagner et al, 1997).…”
Section: Disintegration Of Cell-cell Adhesions and Loss Of Epithelialmentioning
confidence: 99%
“…DP has been studied recently in great detail using homologous recombination to knockout gene function, both tissue specifically and globally. DP has also been knocked down in endothelial cells using siRNA Vasioukhin et al, 2001;Zhou et al, 2004). Each of those investigations clearly demonstrated the importance of DP, especially in the three-dimensional formation of developing epidermis, neurectoderm, heart, and capillaries.…”
Section: Fig 1 Kaz Colocalizes To the Spindle Apparatusmentioning
confidence: 97%