Role of soft tissue and bone interactions in the developmental integration and modularity of the skull in neural crest-specific gap junction alpha-1 knockout mice.

The vertebrate skull is composed of bones derived from neural crest cells and mesoderm. 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- and mesoderm-derived 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-specific gap junction alpha-1 (Gja1) knockout mouse model (Cx43cKO) to determine the effect of tissue origin on skull integration and modularity. Micro-computed tomography images obtained from embryonic, newborn, and 2-month 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-derived frontal bones and mesoderm-derived 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.