Meeting Abstract

16.5  Monday, Jan. 4  Computational approach to neural tube closure VELASQUEZ-CARVAJAL, D.*; SHERARD, K.M.; ROBIN, F.B.; MUNRO , E.M.; University of Washington and University of Antioquia; University of Washington; University of Washington and University of Chicago; University of Washington and University of Chicago davidvelasc@gmail.com

Neural tube closure in ascidians occurs by unidirectional zippering of epithelial and neural tube cells, and involves several distinct cellular processes. On each side of the leading edge of the zipper, filopodia protrude, make contact and pull the edges together until the cells form new adhesions. At the same time, a “V” of localized acto-myosin contractility is progressively activated in just a few cells as they reach the zipper’s leading edge, and experiments inhibiting this contractile “V” demonstrate it is essential for closure. It is not clear how the filopodia, formation of adhesions, and localized contractility work together to generate neural tube closure. We used a two-dimensional computational model in which individual cells could exhibit these behaviors to varying degrees to explore their relative importance. We found that a combination of localized “V” contractility and filopodial action best reproduced the shape changes observed in real embryos. In contrast, uniform purse-string contractility failed to form a long tube, while filopodial action alone was ineffective at sealing the tube. Localized “V” contractility could drive normal closure kinematics, but only a for very restricted set of parameter choices. Further, the model was able to reproduce an experimental observation from partially ablated embryos, in which the “V” had a wider angle than under normal conditions and neural tube closure failed. A concomitance of different cell and tissue conditions are needed for a morphogenetic process to occur properly, and computional modeling provides a means, complementary to experiments, to separate key features essential to such processes.