Cortex Specific Overexpression of BAF170 and Growth of the Cranial Base, Cranial Vault, and Facial Skeleton in Mice

Abstract

The fossil record and craniofacial disease reveal the tight correspondence between brain and skull shape, yet it is not understood how changes in brain growth and consequent changes in brain morphology impact growth of the skull. We tested whether variation in brain size impacted the growth of the cranial base, cranial vault, and facial skeleton in postnatal mice using a transgenic murine model of cortex specific overexpression of Chromatin Remodeling Complex BAF170 Subunit (BAF170cOE) that produces a mouse with a distinctively smaller cerebral cortex. Due to the unique growth mechanisms of the cranial base, cranial vault, and facial skeleton, and their unique anatomic relationships to the cerebral cortex, areas of bone growth may be dissimilarly affected by a reduction in cortical size. Since the cranial vault is anatomically proximate to the cerebral cortex, and because we hypothesized that brain growth impacts skull growth, we anticipated growth of the cranial vault would be more strongly affected relative to growth of the cranial base and facial skeleton. Three dimensional coordinates of landmarks describing the cranial base, cranial vault, and facial skeleton were collected from microcomputed tomography (microCT) images of BAF170cOE mice and unaffected littermates at birth (postnatal day 0 or P0), P14, P28, and P42. Sample sizes ranged between 5 and 10. Growth difference matrix analysis (GDMA) was used to statistically compare growth between genotypes. We found statistically significant differences in cranial vault growth from P0 to P14 between genotypes. There were no significant differences in growth between genotypes for any of the skull modules from P14 to P28 or from P28 to P42. Reduced cortical size of BAF170cOE mice is associated with changes in skull growth during the earliest interval studied here, with significant impacts noted on the growth of the cranial vault. Our results support the hypothesis that brain growth has an effect on skull growth, regardless of the brain decreasing in size. The specificity of the BAF170 Subunit to cause reduced cortical size and lack of direct effect on bone formation allows for future investigation of the mechanisms by which brain and skull growth are integrated.