{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:43:27Z","timestamp":1768509807453,"version":"3.49.0"},"posted":{"date-parts":[[2023,12,4]]},"group-title":"Cell Biology","reference-count":35,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,12,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>AP-2 transcription factors regulate ectodermal development but their roles for epidermal homeostasis in the adult skin are unknown. We find that AP-2\u03b1 is the predominant AP-2 family member in adult epidermis, followed by AP-2\u03b2. Through inactivation of AP-2\u03b1, AP-2\u03b2, or both in keratinocytes we assessed the effects of a gradient of epidermal AP-2 activity on skin function. We find that (1) loss of AP-2\u03b2 in keratinocytes is compensated for by AP-2\u03b1, (2) loss of AP-2\u03b1 impairs terminal keratinocyte differentiation and hair morphogenesis, and (3) the combined loss of AP-2\u03b1\/AP-2\u03b2 results in more severe skin and hair abnormalities. Keratinocyte differentiation defects precede a progressive neutrophilic skin inflammation. Inducible inactivation of AP-2\u03b1\/AP-2\u03b2 in the adult phenocopies these manifestations. Transcriptomic analyses of epidermis lacking AP-2\u03b1 or AP-2\u03b1\/AP-2\u03b2 in keratinocytes demonstrate a terminal keratinocyte differentiation defect with upregulation of alarmin keratins and of several immune pathway regulators. Moreover, our analyses suggest a key role of loss of AP-2\u03b1-dependent gene expression of CXCL14 and KRT15 as an early pathogenic event towards the manifestation of skin inflammation. Thus, AP-2\u03b1\/AP-2\u03b2 are critical regulators of epidermal homeostasis in the adult skin.<\/jats:p>","DOI":"10.1101\/2023.12.03.569763","type":"posted-content","created":{"date-parts":[[2023,12,4]],"date-time":"2023-12-04T16:55:13Z","timestamp":1701708913000},"source":"Crossref","is-referenced-by-count":1,"title":["AP-2\u03b1\/AP-2\u03b2 transcription factors are key regulators of epidermal homeostasis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4936-4791","authenticated-orcid":false,"given":"Hui","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2725-0715","authenticated-orcid":false,"given":"Jackelyn","family":"Raymundo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1346-8747","authenticated-orcid":false,"given":"Kathleen E.","family":"Daly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2724-4825","authenticated-orcid":false,"given":"Wenjuan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5199-2299","authenticated-orcid":false,"given":"Bill","family":"Senapati","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3866-020X","authenticated-orcid":false,"given":"Alexander G.","family":"Marneros","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023120622550859000_2023.12.03.569763v1.1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu170"},{"key":"2023120622550859000_2023.12.03.569763v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2003.10.039"},{"key":"2023120622550859000_2023.12.03.569763v1.3","doi-asserted-by":"crossref","first-page":"106125","DOI":"10.1016\/j.isci.2023.106125","article-title":"GRHL2 and AP2a coordinate early surface ectoderm lineage commitment during development","volume":"26","year":"2023","journal-title":"iScience"},{"key":"2023120622550859000_2023.12.03.569763v1.4","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.22.4775"},{"key":"2023120622550859000_2023.12.03.569763v1.5","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.22002"},{"key":"2023120622550859000_2023.12.03.569763v1.6","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"2023120622550859000_2023.12.03.569763v1.7","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2005-6-13-246"},{"key":"2023120622550859000_2023.12.03.569763v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2010.01.016"},{"key":"2023120622550859000_2023.12.03.569763v1.9","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2002.0597"},{"key":"2023120622550859000_2023.12.03.569763v1.10","first-page":"3895","article-title":"KCTD1 mutants in scalpearnipple syndrome and AP2alpha P59A in Char syndrome reciprocally abrogate their interactions, but can regulate Wnt\/betacatenin signaling","volume":"22","year":"2020","journal-title":"Mol Med Rep"},{"key":"2023120622550859000_2023.12.03.569763v1.11","doi-asserted-by":"crossref","first-page":"2140","DOI":"10.1016\/j.devcel.2023.07.015","article-title":"Molecular and spatial landmarks of early mouse skin development","volume":"58","year":"2023","journal-title":"Dev Cell"},{"key":"2023120622550859000_2023.12.03.569763v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2020.01.012"},{"key":"2023120622550859000_2023.12.03.569763v1.13","doi-asserted-by":"crossref","unstructured":"Kim, J. , Lee, J. , Li, X. , Lee, H.S. , Kim, K. , Chaparala, V. , Murphy, W. , Zhou, W. , Cao, J. , Lowes, M.A. , et al. 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