{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T16:22:27Z","timestamp":1790439747809,"version":"4.1.0"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T00:00:00Z","timestamp":1682294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["LU-1944\/3-1"],"award-info":[{"award-number":["LU-1944\/3-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p><jats:bold>Introduction:<\/jats:bold> Cleft lip \u00b1 cleft palate (CL\/P) is one of the most common birth defects. Although research has identified multiple genetic risk loci for different types of CL\/P (i.e., syndromic or non-syndromic forms), determining the respective causal genes and understanding the relevant functional networks remain challenging. The recent introduction of single-cell RNA sequencing (scRNA-seq) has provided novel opportunities to study gene expression patterns at cellular resolution. The aims of our study were to: (i) aggregate available scRNA-seq data from embryonic mice and provide this as a resource for the craniofacial community; and (ii) demonstrate the value of these data in terms of the investigation of the gene expression patterns of CL\/P candidate genes.<\/jats:p><jats:p><jats:bold>Methods and Results:<\/jats:bold> First, two published scRNA-seq data sets from embryonic mice were re-processed, i.e., data representing the murine time period of craniofacial development: (i) facial data from embryonic day (E) E11.5; and (ii) whole embryo data from E9.5\u2013E13.5 from the Mouse Organogenesis Cell Atlas (MOCA). Marker gene expression analyses demonstrated that at E11.5, the facial data were a high-resolution representation of the MOCA data. Using CL\/P candidate gene lists, distinct groups of genes with specific expression patterns were identified. Among others we identified that a co-expression network including <jats:italic>Irf6, Grhl3<\/jats:italic> and <jats:italic>Tfap2a<\/jats:italic> in the periderm, while it was limited to <jats:italic>Irf6<\/jats:italic> and <jats:italic>Tfap2a<\/jats:italic> in palatal epithelia, cells of the ectodermal surface, and basal cells at the fusion zone. The analyses also demonstrated that additional CL\/P candidate genes (e.g., <jats:italic>Tpm1, Arid3b, Ctnnd1, and Wnt3<\/jats:italic>) were exclusively expressed in <jats:italic>Irf6<\/jats:italic>+ facial epithelial cells (i.e., as opposed to <jats:italic>Irf6-<\/jats:italic> epithelial cells). The MOCA data set was finally used to investigate differences in expression profiles for candidate genes underlying different types of CL\/P. These analyses showed that syndromic CL\/P genes (syCL\/P) were expressed in significantly more cell types than non-syndromic CL\/P candidate genes (nsCL\/P).<\/jats:p><jats:p><jats:bold>Discussion:<\/jats:bold> The present study illustrates how scRNA-seq data can empower research on craniofacial development and disease.<\/jats:p>","DOI":"10.3389\/fcell.2023.1091666","type":"journal-article","created":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T08:48:51Z","timestamp":1682326131000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Analysis of candidate genes for cleft lip \u00b1 cleft palate using murine single-cell expression data"],"prefix":"10.3389","volume":"11","author":[{"given":"Anna","family":"Siewert","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedikt","family":"Reiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carina","family":"Krug","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Heggemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Mangold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henning","family":"Dickten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin U.","family":"Ludwig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,4,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/S0925-4773(00)00518-9","article-title":"Expression of members of the fgf family and their receptors during midfacial development","volume":"100","author":"Bachler","year":"2001","journal-title":"Mech. 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