Ontogenetic and in silico models of spatial-packing in the hypermuscular mouse skull.

Networks linking single genes to multiple phenotypic outcomes can be founded on local anatomical interactions as well as on systemic factors like biochemical products. Here we explore the effects of such interactions by investigating the competing spatial demands of brain and masticatory muscle growth within the hypermuscular myostatin-deficient mouse model and in computational simulations. Mice that lacked both copies of the myostatin gene (-/-) and display gross hypermuscularity, and control mice that had both copies of the myostatin gene (+/+) were sampled at 1, 7, 14 and 28 postnatal days. A total of 48 mice were imaged with standard as well as contrast-enhanced microCT. Size metrics and landmark configurations were collected from the image data and were analysed alongside in silico models of tissue expansion. Findings revealed that: masseter muscle volume was smaller in -/- mice at day 1 but became, and remained thereafter, larger by 7 days; -/- endocranial volumes begin and remained smaller; -/- enlargement of the masticatory muscles was associated with caudolateral displacement of the calvarium, lateral displacement of the zygomatic arches, and slight dorsal deflection of the face and basicranium. Simulations revealed basicranial retroflexion (flattening) and dorsal deflection of the face associated with muscle expansion and abrogative covariations of basicranial flexion and ventral facial deflection associated with endocranial expansion. Our findings support the spatial-packing theory and highlight the importance of understanding the harmony of competing spatial demands that can shape and maintain mammalian skull architecture during ontogeny.