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The evolutionary capacity of the skull has been linked, in part, to the emergence of neural crest cells; however, this increased capacity for evolutionary change requires that variation within neural crest\u2010 and mesoderm\u2010derived bones remains partly autonomous. One way to assess whether tissue origin leads to discrete patterns of variation is through measures of morphological integration and modularity. In this study, we use a neural crest\u2010specific gap junction alpha\u20101 (\n                    <jats:italic>Gja1<\/jats:italic>\n                    ) knockout mouse model (Cx43cKO) to determine the effect of tissue origin on skull integration and modularity. Micro\u2010computed tomography images obtained from embryonic, newborn, and 2\u2010month Cx43cKO and wildtype (Cx43WT) mice were used to measure and compare skull shape, size, integration, and modularity between genotypes. To determine if the phenotypic differences observed between genotypes reflect Cx43 function, mRNA expression data for markers of bone differentiation were measured from the neural crest\u2010derived frontal bones and mesoderm\u2010derived parietal and occipital bones. We found that patterns of integration and modularity change over development and these changes correspond with differences in Cx43 expression throughout the lifespan. Most interestingly, the patterns of developmental integration and modularity we observed at birth were influenced most greatly by tissue interactions, rather than Cx43 expression in the bones. Ultimately, our findings highlight the power of experimental models for investigating integration and modularity and the importance of tissue interactions in skull development.\n                  <\/jats:p>","DOI":"10.1002\/ar.70115","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T14:11:06Z","timestamp":1766153466000},"page":"3375-3396","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Role of soft tissue and bone interactions in the developmental integration and modularity of the skull in neural crest\u2010specific gap junction alpha\u20101 knockout mice"],"prefix":"10.1002","volume":"309","author":[{"given":"Alyssa C.","family":"Moore","sequence":"first","affiliation":[{"name":"Department of Anatomy and Cell Biology University of Western Ontario  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline","family":"Tourigny","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology University of Western Ontario  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Quinonez","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology University of Western Ontario  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Barr","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology University of Western Ontario  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew W.","family":"Grol","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology University of Western Ontario  London Ontario Canada"},{"name":"Bone and Joint Institute University of Western Ontario  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8563-3354","authenticated-orcid":false,"given":"Katherine E.","family":"Willmore","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology University of Western Ontario  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,19]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"Adams D. 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