Meeting Abstract

LBS2.3  Thursday, Jan. 3  A Novel Transgenic Mouse Model for Fetal Encephalization and Craniofacial Development NICHOLSON, Elisabeth K.*; STOCK, Stuart R.; CHENN, Anjen; RAVOSA, Matthew J.; Northwestern Univ. Feinberg Sch. of Med.; NU Feinberg Sch. of Med.; NU Feinberg Sch. of Med.; Univ. of Missouri Sch. of Med. e-nicholson@northwestern.edu

There are surprisingly few experimental models of neural growth and cranial integration. This and the dearth of information regarding fetal brain development detract from our understanding of cranial integration and its relevance to the ontogenetic and interspecific patterning of skull form. 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 precursors, 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 interrelationships are established in the skull.
Comparisons of wild-type and transgenic mice were performed using microCT, MRI and histology. These analyses show that the larger brain of the transgenic mice is associated with a rounded neurocranium, a more flexed basicranium and a shorter facial skull. The transgenic mice also develop longer and taller skulls, wider presphenoid bones and shorter faces and nasal bones. Comparisons of the rate of postcranial and cranial ossification also point to an unexpected effect of neural growth on skull development: increased fetal encephalization apparently results 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.