Genetics and Developmental Biology of Closed Dysraphic Conditions
Closed spinal dysraphic conditions are typically considered malformations of caudal development and have prompted intense speculation on possible pathogenic mechanisms. Ultimately, an understanding of developmental processes, both normal and abnormal, requires an experimental evidence base. This chapter surveys the experimental literature for clues to the genetics and developmental biology of human spinal dysraphism, based largely on studies in mouse models. Current trends in human disease gene identification, and the development of mouse genetic disease models are reviewed, as well as several key areas of developmental biology progress that relate to development of the caudal body axis. Open neural tube defects (e.g. myelomeningocele) are relatively well understood owing to the many mouse models of faulty neural tube closure. Closed lesions in which the spinal cord is tethered and associated with spinal lipoma are much less well represented in mouse models; only preliminary clues to their likely developmental origins can currently be discerned. Some closed sacro-caudal conditions have a more defined genetic and developmental biology basis, for example dorsal and ventral vertebral anomalies, caudal regression syndrome and Currarino triad. A future concerted research effort is needed to bring together clinical observations with research in developmental biology in this important area of paediatric clinical management.
KeywordsDevelopmental biology Genetics Neural tube Neurulation Mouse models Malformations Spinal cord Notochord Vertebrae
The authors thank Ms. Lenka Filipkova for the embryo image in Fig. 21.1. The authors’ research on spinal dysraphism is supported by grants from Smiles with Grace, Great Ormond Street Hospital Children’s Charity (GOSHCC) and a Child Health Research PhD studentship. AC and NG are GOSHCC Professors.
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