Loss of AP-2α impacts multiple aspects of ventral body wall development and closure

Abstract

Human birth defects involving the ventral body wall are common, yet little is known about the mechanism of body wall closure in mammals. The AP-2α transcription factor knock-out mouse provides an exceptional tool to understand this particular pathology, since it has one of the most severe ventral body wall closure defects, thoracoabdominoschisis. To gain insight into the complex morphological events responsible for body wall closure, we have studied this developmental process in AP-2α knock-out mice. Several tissues involved in normal ventral body wall closure are defective in the absence of AP-2α, including those associated with the primary body wall, the umbilical ring, and the mesoderm of the secondary body wall. These defects, coupled with the expression pattern of AP-2α, suggest that AP-2α is involved in multiple developmental mechanisms directing the morphogenesis of the ventral body wall, including cell migration, differentiation, and death. There is a failure of migration and fusion of the body folds at the umbilical ring, as well as in the formation and migration of the abdominal bands and ventral musculature. Furthermore, the mechanism of cell deposition at the umbilical ring is disturbed. Consequently, the mesodermal compartment of the body wall is underdeveloped. We also suggest that AP-2α is required for signaling from the surface ectoderm to the underlying mesoderm for proper development and closure of the ventral body wall. These findings provide a fundamental understanding of how AP-2α functions in the closure of the ventral body wall, as well as offer insight into related human birth defects.