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This study aimed to clarify the identity of this ill-defined cell type. Ultrastructurally, all cells with tightly packed microvilli observed in the tracheal epithelium of <jats:italic>Pou2f3<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>-mice contained basally located dense core vesicles, a characteristic feature of neuroendocrine cells (NEC). Accordingly, immunofluorescence double-labeling utilizing NEC markers revealed villin-labeling in two thirds of NEC in the trachea, a reporter mouse strain showed Cre recombinase activity driven by the <jats:italic>Vil1<\/jats:italic> promoter in a subpopulation of tracheal NEC, and analysis of single cell RNA sequencing data revealed <jats:italic>Vil1<\/jats:italic>-mRNA expression by tracheal NEC. Notably, only a minimal fraction (\u22481%) of bronchopulmonary NEC (solitary and clustered in neuroepithelial bodies) displayed villin-immunoreactivity, despite nearly half of them having a history of <jats:italic>Vil1<\/jats:italic> promoter activity. Microvilli of tuft cells differed ultrastructurally from those of NEC, and the majority of tuft cells were immunoreactive to advillin (<jats:italic>Avil<\/jats:italic>), showed <jats:italic>Avil<\/jats:italic> promoter activity as indicated by a reporter mouse strain, and expressed Avil-mRNA in the sequencing data set. This study uncovers villin-expressing cells in the lower airways as a cell population hidden among NEC. Advillin, not villin, is identified as a marker for airway tuft cells. This should be considered in interpreting findings based on the use of villin as a marker or Cre-driver when investigating rare cells in the murine airways.<\/jats:p>\n          <jats:p>\n            <jats:bold>Graphical Abstract<\/jats:bold>\n          <\/jats:p>\n          <jats:p>In mice, neuroendocrine cells express villin and persist in Pou2f3-deficient mice. Tuft cells, on the other hand, express advillin and are absent in Pou2f3-deficient mice.<\/jats:p>","DOI":"10.1007\/s00441-025-04003-y","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T03:12:42Z","timestamp":1756696362000},"page":"1-20","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Differential expression of villin and advillin by neuroendocrine and tuft cells in the murine lower airways"],"prefix":"10.1007","volume":"402","author":[{"given":"Wafaa","family":"Mahmoud","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Perniss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krupali","family":"Poharkar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maryam","family":"Keshavarz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrich","family":"G\u00e4rtner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes","family":"Oberwinkler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Burkhard","family":"Sch\u00fctz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Worzfeld","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Offermanns","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang","family":"Kummer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,9,1]]},"reference":[{"key":"4003_CR1","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1016\/S0022-5320(65)80055-7","volume":"12","author":"KG Bensch","year":"1965","unstructured":"Bensch KG, Gordon GB, Miller LR (1965) Studies on the bronchial counterpart of the Kultschitzky (argentaffin) cell and innervation of bronchial glands. 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