Mouse models for the study of cranial base growth and anomalies

Abstract

The cranial base is a central and integral component of the cranioskeleton, yet little is known about its growth. Despite the dissimilarities between human and murine cranioskeletal form, mouse models are proving instrumental in studying craniofacial growth. The objectives of this review are to summarize recent findings from numerous mouse models that display growth defects in one or more cranial base synchondroses, with accompanying changes in chondrocyte cellular zones. Many of these models also display altered growth of the cranial vault and/or the facial region. FGFR, PTHrP, Ihh, BMP and Wnt/β-catenin, as well as components of primary cilia, are the major genes and signalling pathways identified in cranial base synchondroses. Together, these models are helping to uncover specific genetic influences and signalling pathways operational at the cranial base synchondroses. Many of these genes are in common with those of importance in the cranial vault and the facial skeleton, emphasizing the molecular integration of growth between the cranial base and other cranial regions. Selected models are also being utilized in testing therapeutic agents to correct defective craniofacial and cranial base growth.

Keywords: cranial base; craniofacial anomalies; craniofacial genetics; mouse models; synchondroses.