Morphogenesis of the cervical vertebrae : a computer investigation into developmental mechanisms
In mammals the presence of a vertebral column defines the phylum and provides protection and support for essential organ systems such as those of respiration, locomotion and neurological function. Congenital abnormalities of the vertebral column in the human are uncommon but they can lead to spinal instability and accelerated degenerative change. They are also often associated with other system abnormalities. Because our understanding of the developmental process is incomplete, and there is little clinical and / or scientific evidence on which treatment decisions can be based, it is difficult for doctors to decide on the best treatment for affected individuals. With this in mind, the aim of this work has been to construct a theoretical model of vertebral body morphogenesis in order to investigate and clarify mechanisms of normal development and how they might be altered in the formation of congenitally abnormal vertebrae. As a first step a classification system of vertebral malformations was developed from a study of the clinical and scientific literature. Using cellular automata techniques on a personal computer a model of vertebral body morphogenesis was then constructed and this was used to generate and test hypotheses regarding the aetiology of the observed malformations. The results of this work suggest that during normal development: (i) sclerotomal cells migrate medially without significant cranial or caudal deviation (ii) cellular replication is necessary for normal formation of the cellular condensation which will ultimately develop into the vertebral body. Abnormal vertebrae were found to be a consequence of (i) abnormal spatial arrangement of the sclerotomal cells resulting from malsegmentation of the paraxial mesoderm or (ii) decreased or absent sclerotomal cell replication The causes of the malsegmentation and abnormal cellular replication in the human embryo is not certain. However animal models have suggested exposure to common environmental teratogens such as sodium valproate and alcohol can cause malsegmentation before the embryo's mother even realises she is pregnant.