Development, tissue origins, and variation of the mouse cranial base

The cranial base is a complex skeletal structure centrally located in the cranium, and its development has not been studied extensively in the mouse, a popular model organism for craniofacial research. This dissertation examines the development and tissue origins of the mouse chondrocranium in order to test if all cartilages of the anterior cranial base are derived from neural crest cells. This dissertation also investigates normal and abnormal developmental processes in order to test how variation in length and width of the chondrocranium is correlated with variation in mature cranial base shape. This thesis found that cranial base cartilages develop in a temporal and spatial pattern that is unique to the mouse, and the murine chondrocranium is fully formed by embryonic day 16. Furthermore, the New Head Hypothesis (Gans & Northcutt, 1983; Gans, 1993; Northcutt, 2005) is supported as nearly all prechordal cartilages are derived from neural crest cells, with the exception of the hypochiasmatic cartilages, which are likely derived from prechordal plate mesoderm in close association with the extrinsic ocular muscles. This dissertation also examines cranial base development in the Brachyrrhine (Br) mouse. Six2 expression is greatly decreased in Br/Br mutant mice, which have absent orbital cartilages and malformed trabecular cartilages, eventually leading to a clefted midface, hypertelorism, a wide nasal capsule, and death shortly after birth. Finally, this dissertation tests how variation observed in mature cranial base morphology for three inbred mouse strains is correlated with variation in chondrocranium shape and alterations in developmental processes. DBA/2J mice have an abnormally fused presphenoidal synchondrosis. Relative to C57BL/6J mice, adult A/J mice have a relatively narrow presphenoidal synchondrosis, which correlates with a relatively narrow caudal trabecular cartilage. Furthermore, fewer mesenchymal stern cells contribute to the trabecular condensation in A/J mice, suggesting that at least this cellular process may be an important factor contributing to alterations in mature cranial base element width as predicted by the Atchley and Hall (1991) model. The research in this dissertation has laid the foundation for future analyses of the relationship between developmental genetics and anatomical structure of the cranial base in mice.