Immotile cilia at the ventral node of mouse embryos are required for sensing leftward fluid flow that breaks left-right symmetry of the body. However, the flow-sensing mechanism has long remained elusive. In this work, we show that immotile cilia at the node undergo asymmetric deformation along the dorsoventral axis in response to the flow. Application of mechanical stimuli to immotile cilia by optical tweezers induced calcium ion transients and degradation of Dand5 messenger RNA (mRNA) in the targeted cells. The Pkd2 channel protein was preferentially localized to the dorsal side of immotile cilia, and calcium ion transients were preferentially induced by mechanical stimuli directed toward the ventral side. Our results uncover the biophysical mechanism by which immotile cilia at the node sense the direction of fluid flow.

SignificanceEach neuron forms a single axon and multiple dendrites, and this configuration is important for wiring the brain. How only a single axon extends from a neuron, however, remains unknown. This study demonstrates that CAMSAP3, a protein that binds the minus-end of microtubules, preferentially localizes along axons in hippocampal neurons. Remarkably, mutations of CAMSAP3 lead to production of multiple axons in these neurons. In attempts to uncover mechanisms underlying this abnormal axon extension, the authors found that CAMSAP3-anchored microtubules escape from acetylation, a process mediated by α-tubulin acetyltransferase-1, and depletion of this enzyme abolishes abnormal axon formation in CAMSAP3 mutants. These findings reveal that CAMSAP3 controls microtubule dynamics, preventing tubulin acetylation; this mechanism is required for single-axon formation.

Cell migration plays a pivotal role in morphogenetic and pathogenetic processes. To achieve directional migration, cells must establish a front-to-rear axis of polarity. Here we show that components of the cadherin-catenin complex function to stabilize this front-rear polarity. Neural crest and glioblastoma cells undergo directional migration in vivo or in vitro. During this process, αE-catenin accumulated at lamellipodial membranes and then moved toward the rear with the support of a tyrosine-phosphorylated β-catenin. This relocating αE-catenin bound to p115RhoGEF, leading to gathering of active RhoA in front of the nucleus where myosin-IIB arcs assemble. When catenins or p115RhoGEF were removed, cells lost the polarized myosin-IIB assembly, as well as the capability for directional movement. These results suggest that, apart from its well-known function in cell adhesion, the β-catenin/αE-catenin complex regulates directional cell migration by restricting active RhoA to perinuclear regions and controlling myosin-IIB dynamics at these sites.

Nishimura et al. show that DAAM1, a formin family actin polymerization regulator, stabilizes epithelial cell junctions by counteracting the WAVE complex, another actin regulator. Loss of DAAM1 promotes the motility of junctional membranes and thereby enhances their invasion of neighboring environments.

Collective migration of epithelial cells plays crucial roles in various biological processes such as cancer invasion. In migrating epithelial sheets, leader cells form lamellipodia to advance, and follower cells also form similar motile apparatus at cell–cell boundaries, which are called cryptic lamellipodia (c-lamellipodia). Using adenocarcinoma-derived epithelial cells, we investigated how c-lamellipodia form and found that they sporadically grew from around E-cadherin–based adherens junctions (AJs). WAVE and Arp2/3 complexes were localized along the AJs, and silencing them not only interfered with c-lamellipodia formation but also prevented follower cells from trailing the leaders. Disruption of AJs by removing αE-catenin resulted in uncontrolled c-lamellipodia growth, and this was brought about by myosin II activation and the resultant contraction of AJ-associated actomyosin cables. Additional observations indicated that c-lamellipodia tended to grow at mechanically weak sites of the junction. We conclude that AJs not only tie cells together but also support c-lamellipodia formation by recruiting actin regulators, enabling epithelial cells to undergo ordered collective migration.