Increased prenatal brain growth in a transgenic mouse model decreases cranial development: An expensive tissue hypothesis for the skull

In vertebrates, it has been argued that the development and evolution of an enlarged brain requires an increased basal metabolic rate or a compensatory reduction in the resources devoted to the formation of other metabolically costly tissues, leading to a reduction in the size of such organs. While the latter scenario is indirectly supported by comparative data, especially in primates, this inherently ontogenetic phenomenon has not been addressed in a mechanistic framework. Our experimental study investigates the relationship between brain growth and cranial development in ß-catenin transgenic mice with remarkably increased levels of prenatal neurogenesis. To evaluate associated changes in skull form and control for variation in maternal resources among mouse litters, we directly compare data from transgenic and wild-type littermates. Ossification patterns in the limbs and skull were also analyzed to control for within-subject variation in skeletal formation. Transgenic mice, with relatively larger brains, are characterized by a corresponding decrease in the degree of cranial ossification for a given age, in contrast to the presence of similar rates of postcranial ossification between transgenic and wild-type mice. This disparity is most pronounced in the neurocranial vault, which is supplied by a greater number of vessels in common with the brain than the facial skull. Mice with relatively larger brains had a decrease in cranial ossification. As modern humans are more encephalized than living apes and most extinct hominids, our findings provide unique insights into hominid evolution, particularly the “expensive tissue hypothesis” regarding energetic tradeoffs during neural and cranial development.