{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T23:04:15Z","timestamp":1790723055405,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T00:00:00Z","timestamp":1663286400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP142344"],"award-info":[{"award-number":["MOP142344"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["anatomypubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Developmental Dynamics"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Glypicans are a family of proteoglycans that play important roles in embryonic morphogenesis. The mammalian genome contains six glypicans (<jats:italic>GPC1<\/jats:italic> to <jats:italic>GPC6<\/jats:italic>). GPC6 and GPC4 are the pair of glypicans that show the highest degree of homology within the family. <jats:italic>GPC6<\/jats:italic>\u2010null embryos display bone abnormalities and severely shortened intestines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We show that <jats:italic>GPC6<\/jats:italic>\u2010null embryos display significantly smaller stomachs, and that Hedgehog and noncanonical Wnt signaling are dysregulated in GPC6\u2010null stomachs. Like GPC6, GPC4 is expressed by the developing stomach. However, <jats:italic>GPC4<\/jats:italic>\u2010null embryos have normal stomachs. To investigate whether GPC6 and GPC4 display functional overlap in the developing stomach, we crossed <jats:italic>GPC4<\/jats:italic>\u2010null mice with <jats:italic>GPC6<\/jats:italic> conditional mutants in which the expression of this glypican is severely reduced in the stomach. Notably, we found that the compound mutants display stomachs that are smaller than those of the <jats:italic>GPC6<\/jats:italic> conditional mutants. We also found that this functional overlap between GPC6 and GPC4 is mediated by the noncanonical Wnt pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study demonstrates that GPC6 stimulates the growth of the embryonic stomach via Wnt and Hh signaling. In addition, we uncovered a Wnt\u2010mediated functional overlap between GPC6 and GPC4 in the developing stomach.<\/jats:p><\/jats:sec>","DOI":"10.1002\/dvdy.533","type":"journal-article","created":{"date-parts":[[2022,9,4]],"date-time":"2022-09-04T12:48:25Z","timestamp":1662295705000},"page":"2015-2028","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Glypican\u20106 and Glypican\u20104 stimulate embryonic stomach growth by regulating Hedgehog and noncanonical Wnt signaling"],"prefix":"10.1002","volume":"251","author":[{"given":"Wen","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Medical Biophysics, Sunnybrook Research Institute University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9786-0426","authenticated-orcid":false,"given":"Jorge","family":"Filmus","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics, Sunnybrook Research Institute University of Toronto  Toronto Ontario 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