Do lamellipodia have the mechanical capacity to drive convergent extension?

Abstract

Convergent extension (CE), a kinematic motif associated with several important morphogenetic movements in embryos, entails narrowing of a tissue in one in-plane direction and elongation in the other. Although the cell elongation and intercalation which accompany this process have been investigated and relevant genes and biochemical pathways have been studied in multiple organisms, a fundamental question that has not yet been answered is "Do the lamellipodia thought to drive these motions actually have the mechanical capacity to do so?" Here, we address this and a number of related issues using a state-of-the-art computational model which can replicate cell motions, changes in cell shape and tissue deformations. The model is based on the cell-level finite element approach of Chen and Brodland, but has additional features which allow it to model lamellipodium formation and contraction. In studying CE, computational models provide an important complement to molecular approaches because they reveal the "mechanical pathways" through which gene products must ultimately act in order to produce physical movements. The model shows that lamellipodia can drive CE, that they do so through cell intercalations and that the elongated cells characteristic of CE arise only when adjacent tissues resist convergence, a result which we confirm experimentally.