PhD

dissertationFollowing gastrulation, the vertebrate hindbrain is transiently segmented into 7 or 8 compartments termed rhombomeres. These compartments play a critical role in the organization of the motor and sensory components of the cranial nerves of the hindbrain. In addition, they are vital to the organization and patterning of the rhombencephalic neural crest, a population of cells that contributes heavily to the formation of craniofacial and pharyngeal structures as well as the ventral body wall. Within the past decade, a number of genes have been identified that function within, and are expressed in segmental fashion along, the embryonic vertebrate hindbrain. Among these are the 3', or anteriorly expressed, members of the Hox gene family. The work presented in this study is an examination of the individual and collective function of four 3' Hox genes, Hoxa1, Hoxa2, Hoxb1 and Hoxb2, in patterning the hindbrain. To accomplish these studies, mice harboring mutations at each of these loci were generated via standard gene targeting techniques and were bred to generate embryos lacking individual or various combinations of these Hox genes. The effects of these mutations on patterning the hindbrain were investigated as well as corresponding defects in the cranial nerves, craniofacial structures, and ventral body wall. The results of these studies provide valuable insights into the importance of hindbrain patterning on neuronal and craniofacial development as well as the mechanisms by which human birth defects such as cleft palate, facial paralysis, and split sternum occur