{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:59:49Z","timestamp":1791219589943,"version":"4.1.0"},"posted":{"date-parts":[[2026,9,30]]},"group-title":"Cell Biology","reference-count":57,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["R01 AR041836"],"award-info":[{"award-number":["R01 AR041836"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01 AR043380"],"award-info":[{"award-number":["R01 AR043380"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01 CA228196"],"award-info":[{"award-number":["R01 CA228196"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["F31 AR086611"],"award-info":[{"award-number":["F31 AR086611"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01 HD107841"],"award-info":[{"award-number":["R01 HD107841"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01 AR081103"],"award-info":[{"award-number":["R01 AR081103"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Skin development depends on coordinated biochemical and mechanical signaling to form a multilayered epidermal barrier. Our previous work demonstrated that the stratified tissue-specific desmosomal cadherin Desmoglein-1 (Dsg1) promotes epidermal differentiation in human\n                  <jats:italic>in vitro<\/jats:italic>\n                  models. Dsg1 first appears in the developing mouse epidermis around E14, coinciding with a developmental transition in stratification and the onset of terminal differentiation, raising the question of how Dsg1 contributes to epidermal morphogenesis\n                  <jats:italic>in vivo<\/jats:italic>\n                  . We generated a wild-type (WT) single-cell RNA sequencing (scRNA-seq) atlas of murine skin and integrated scRNA-seq data from Dsg1 knockout (Dsg1 KO) embryos spanning E14.5, E15.5, E16.5, and E18.5. Six keratinocyte subpopulations were annotated, including a Transitional subpopulation co-expressing basal and suprabasal markers, positioned between basal and differentiated states. Dsg1 KO epidermis exhibited reduced thickness at E14.5-E15.5, but recovered by E16.5-E18.5, suggesting compensatory adaptation. Differential gene expression analysis revealed enrichment of cell-cycle and actin-associated programs in Dsg1 KO during late development. EdU incorporation and PCNA staining confirmed increased proliferation in superficial layers accompanied by altered actin organization and changed cell morphology. Notably, actin and the Arp2\/3 actin nucleation-promoting factor N-WASP exhibited marked changes in distribution during early and late development, respectively. Mechanistically, Dsg1 associates with Nck1, an adaptor linking N-WASP to Arp2\/3-dependent actin polymerization. Silencing Nck1 or N-WASP reduced Dsg1-mediated stratification significantly, while a Nck1-binding-deficient Dsg1 mutant failed to rescue stratification in Dsg1-deficient keratinocytes\n                  <jats:italic>in vitro<\/jats:italic>\n                  . Together, these findings identify a Dsg1-Nck1-N-WASP axis linking desmosomal adhesion to cytoskeletal remodeling and support a model in which Dsg1 coordinates cell-cycle, cell morphology, and actin dynamics to drive epidermal morphogenesis.\n                <\/jats:p>","DOI":"10.64898\/2026.09.29.755418","type":"posted-content","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:30:20Z","timestamp":1790789420000},"source":"Crossref","is-referenced-by-count":0,"title":["Desmoglein-1 coordinates cell proliferation and actin dynamics to promote epidermal morphogenesis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-0768-204X","authenticated-orcid":false,"given":"Brieanna L.","family":"Jarrell","sequence":"first","affiliation":[{"name":"Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA"},{"name":"Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4843-0168","authenticated-orcid":false,"given":"Robert","family":"Harmon","sequence":"additional","affiliation":[{"name":"Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6618-3976","authenticated-orcid":false,"given":"Xin","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7588-4726","authenticated-orcid":false,"given":"Jennifer L.","family":"Koetsier","sequence":"additional","affiliation":[{"name":"Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, 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