Speaker: Dr. Erina Kuranaga
(Team Leader, RIKEN Center for Developmental Biology; 2016.4~ Professor, Graduate School of Life Sciences, Tohoku Univ.)
Title: “Collective Movement of Epithelial Cells Regulated by Left-Right Asymmetric Cell Polarity in Clockwise Morphogenesis”
The collective migration of cohesive cells is a key process involved in epithelial morphogenesis, wound healing, and cancer metastasis. Collective cell migration is thought to respond to cell-extrinsic chemoattractants sensed by the leading edge of a moving cell cluster, however, how cells even non-leader cells synchronously or collectively move towards the same direction is less understood. Here, we describe an alternative mechanism occurring during Drosophila development that requires the generation of local left-right (LR) asymmetric mechanical force within the apical plane of epithelial cells. During the morphogenesis of Drosophila male terminalia, the genitalia undergo a 360˚ clockwise rotation, inducing dextral spermiduct looping. While genitalia rotation involves the rotation of surrounding epithelial tissue during metamorphosis, the underlying mechanistic details have remained unclear. We found that individual epithelial cells surrounding the genitalia adopt LR asymmetric polarity within their apical plane, termed planar cell-shape chirality (PCC), which was discovered as an intrinsic cellular process. An intact PCC can determine the clockwise genitalia rotation because myosinID (myoID) mutant, which shows counter-clockwise genitalia rotation, exhibited reversed PCC in surrounding epithelial cells. Moreover, using live imaging analysis we found that the epithelial cells migrated collectively, resulting in epithelial tissue rotation. The migrating cells exhibited cell junction remodelling, while remaining attached to their neighbours through adherence junctions. Most of the remodelled cell boundaries formed a right oblique angle with the anterior-posterior axis, and were associated with Myosin-II accumulation at right oblique cell boundaries during genitalia rotation. The LR asymmetric distribution of Myosin-II was reversed in flies expressing myoID dsRNA. Numerical simulations showed that LR asymmetric contractility and junction remodelling were sufficient to induce the collective cell migration in virtual 2D tissues. These findings provide new mechanistic insight into the directional collective cell movement that induces the LR asymmetric morphogenesis of epithelial tissue, which is different from conventional guidance-mediated cell movement.
* This seminar will be held in English.