Integrative and Comparative Biology Advance Access published online on July 9, 2008
Integrative and Comparative Biology, doi:10.1093/icb/icn047
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A novel transgenic mouse model of fetal encephalization and craniofacial development
*Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine; Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Feinberg School of Medicine, Chicago, IL 60614, USA; Department of Pharmacology, Graduate School of Medicine, Kyoto University, Yoshida-Konoé-cho, Sakyo, Kyoto 606-8501, Japan; Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60614, USA; #Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, Columbia, MO 65212, USA
Correspondence: 1E-mail: ravosam{at}health.missouri.edu
There are surprisingly few experimental models of neural growth and cranial integration. This, and the dearth of information regarding fetal brain development, detracts from a mechanistic understanding of cranial integration and its relevance to the ontogenetic and interspecific patterning of the form of the skull. To address this shortcoming, our research uses transgenic mice expressing a stabilized form of β-catenin to isolate the effects of encephalization on the development of the basi- and neuro-cranium. These mice develop highly enlarged brains due to an increase in neural precursor cells, and differences between transgenic and wild-type mice are predicted to result solely from variation in relative brain size. By focusing on prenatal growth, this project adds to our understanding of a critically important period when major structural and functional interrelationships are established in the skull. Comparisons of wild-type and transgenic mice were performed using microcomputed tomography (microCT) and magnetic resonance imaging (MRI). These analyses show that the larger brains of the transgenic mice are associated with a larger neurocranium and an altered basicranial morphology. However, body size and postcranial ossification do not seem to be affected by the transgene. Comparisons of the rate of postcranial and cranial ossification also point to an unexpected effect of neural growth on skull development: increased fetal encephalization may result in a compensatory decrease in the level of cranial ossification. Therefore, if other life-history factors are held constant, the ontogeny of a metabolically costly structure, such as a brain, may occur at the expense of other cranial structures. These analyses indicate the benefits of a multifactorial approach to cranial integration using a mouse model.
From the symposium "Building a Better Organismal Model: The Role of the Mouse" presented at the annual meeting of the Society for Integrative and Comparative Biology, January 2-6, 2008, at San Antonio, Texas.