Abstracts of papers presented at the sixteenth Genetics Society's Mammalian Genetics and Development Workshop held at the Institute of Child Health, University College London on 21 and 22 November 2005

Extract

Prior to cranial neural tube closure, the neural folds adopt a biconvex morphology which is thought to be due to expansion of the underlying mesenchyme. Dorso-lateral hinge points (DLHPs) then form, which allow the dorsal tips of the neural folds to ‘flip around’ resulting in apposition of the tips and facilitating subsequent fusion. Cranial closure is particularly prone to perturbation, leading to exencephaly in many mouse mutants and as a result of a variety of teratogenic influences. This may reflect mechanical tensions affecting the closing cranial neural folds. For example, the presence of ventral flexures of the body axis at the mid- and forebrain levels mechanically opposes the formation of DLHPs. Several processes have been implicated as important in overcoming these mechanical tensions, thereby assisting in cranial neural tube closure. These include contraction of actin microfilaments at the luminal surface of the neuroepithelium and apoptosis in the dorsal and dorsolateral neuroepithelium. The latter may act to increase flexibility in the dorsal neural folds, enhancing DLHP formation. Neural crest cells (NCC) originate in the dorsal tips of the neuroepithelium and undergo an epithelial-to-mesenchymal transition, allowing them to delaminate, exit the neuroepithelium and migrate extensively throughout the embryo to form numerous derivatives. We hypothesized that delamination of the NCC from the neuroepithelium may enhance the mechanical flexibility of the dorsal tips of the neural folds, allowing the ‘flip around’ event to occur.