{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T05:00:59Z","timestamp":1773032459064,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100018623","name":"Quanzhou City Science and Technology Program","doi-asserted-by":"publisher","award":["2025QZNY014"],"award-info":[{"award-number":["2025QZNY014"]}],"id":[{"id":"10.13039\/501100018623","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genesis"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The development of the mouse submandibular gland (SMG) is a classic model for branching morphogenesis, orchestrated by key signaling pathways such as Hedgehog (Hh) and Wnt. While Sonic Hedgehog (Shh) is known to be essential for early SMG development, its downstream mechanisms and potential crosstalk with other pathways remain unclear. This study investigates the functional interaction between Hh and Wnt signaling during SMG morphogenesis. Using both in\u00a0vivo (pharmacological inhibition in pregnant mice) and ex\u00a0vivo (organ culture) models, we inhibited Hh signaling with vismodegib from embryonic day 13.5 (E13.5). Hh inhibition led to severe morphological defects, including reduced epithelial branching and disorganized ductal structures. As expected, the expression of Hh target genes Ptch1 and Gli1 was downregulated. Notably, Hh suppression resulted in a concomitant upregulation of Wnt pathway activity, evidenced by increased nuclear \u03b2\u2010catenin and elevated expression of the target genes Axin2 and Lef1. This suggested that Hh signaling normally acts to repress Wnt activity during SMG development. Critically, the co\u2010administration of the Wnt inhibitor XAV939 with vismodegib in ex\u00a0vivo cultures partially rescued the branching defects caused by Hh inhibition. We conclude that Hh signaling promotes murine SMG morphogenesis, at least in part, by tonically inhibiting the Wnt pathway. This study unveils a novel inhibitory crosstalk between Hh and Wnt signaling that is essential for normal salivary gland development.<\/jats:p>","DOI":"10.1002\/dvg.70042","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T11:50:50Z","timestamp":1768909850000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hedgehog\u2010Wnt Crosstalk Orchestrates Submandibular Gland Morphogenesis in Mice"],"prefix":"10.1002","volume":"64","author":[{"given":"Yunhong","family":"Song","sequence":"first","affiliation":[{"name":"School of Stomatology, Quanzhou Medical College  Quanzhou Fujian China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yamin","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Public Health, Quanzhou Medical College  Quanzhou Fujian China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Stomatology, Quanzhou Medical College  Quanzhou Fujian China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donghai","family":"Qiu","sequence":"additional","affiliation":[{"name":"School of Stomatology, Quanzhou Medical College  Quanzhou Fujian China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Stomatology, Quanzhou Medical College  Quanzhou Fujian China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3622-1350","authenticated-orcid":false,"given":"Yan","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Stomatology, Quanzhou Medical College  Quanzhou Fujian China"},{"name":"Medical Research Center of Quanzhou Medical College, Quanzhou Medical College  Quanzhou Fujian China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.012054"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/383407a0"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2017.7030"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.24627"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1387\/ijdb.200307lg"},{"key":"e_1_2_10_7_1","first-page":"458","article-title":"Sonic Hedgehog Contributes to Lumen Formation and Epithelial Polarization in Developing Salivary Glands","volume":"295","author":"Hashizume K.","year":"2006","journal-title":"Developmental Biology"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00172"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.938601"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-213X-5-11"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(98)00062-8"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.10472"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0185(19991101)256:3<252::AID-AR5>3.0.CO;2-6"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1159\/000046183"},{"key":"e_1_2_10_15_1","first-page":"487","article-title":"Embryonic Submandibular Gland Branching Morphogenesis Requires FGF8 Signaling","volume":"271","author":"Jaskoll T.","year":"2004","journal-title":"Developmental Biology"},{"key":"e_1_2_10_16_1","first-page":"639","article-title":"EGF Receptor Ligands in the Submandibular Gland of the Mouse","volume":"39","author":"Kashimata M.","year":"1997","journal-title":"Development, Growth & Differentiation"},{"key":"e_1_2_10_17_1","first-page":"818","article-title":"Submandibular Gland Organogenesis and the Origins of Salivary Gland Stem Cells Wiley Interdisciplinary Reviews","volume":"1","author":"Knosp W. 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