Alignment of the cell long axis by unidirectional tension acts cooperatively with Wnt signalling to establish planar cell polarity.

Planar cell polarity (PCP) is the aligned cell polarity within a tissue plane. Mechanical signals are known to act as a global cue for PCP, yet their exact role is still unclear. In this study, we focused on PCP in the posterior neuroectoderm of Xenopus laevis and investigated how mechanical signals regulate polarity. We reveal that the neuroectoderm is under a greater tension in the anterior-posterior direction and that perturbation of this tension causes PCP disappearance. We show that application of uniaxial stretch to explant tissues can control the orientation of PCP and that cells sense the tissue stretch indirectly through a change in their shape, rather than directly through detection of anisotropic tension. Furthermore, we reveal that PCP is most strongly established when the orientation of tissue stretch coincides with that of diffusion of locally expressed Wnt ligands, suggesting a cooperative relationship between these two PCP regulators.

Fam46a regulates BMP-dependent pre-placodal ectoderm differentiation in Xenopus.

The pre-placodal ectoderm (PPE) is a specialized ectodermal region which gives rise to the sensory organs and other systems. The PPE is induced from the neural plate border during neurulation, but the molecular mechanism of PPE formation is not fully understood. In this study, we examined the role of a newly identified PPE gene, Fam46a, during embryogenesis. Fam46a contains a nucleoside triphosphate transferase domain, but its function in early development was previously unclear. We show that Fam46a is expressed in the PPE in Xenopus embryos, and Fam46a knockdown induces abnormalities in the eye formation and the body color. At the neurula stage, Fam46a upregulates the expression of PPE genes and inhibits neural crest formation. We also show that Fam46a physically interacts with Smad1/Smad4 and positively regulates BMP signaling. From these results, we conclude that Fam46a is required for PPE formation via the positive regulation of BMP signaling. Our study provides a new mechanism of ectodermal patterning via cell-autonomous regulation of BMP signaling in the PPE.

FRET-based tension measurement across actin-associated mechanotransductive structures using Lima1.

During embryogenesis, mechanical forces play important roles in morphogenesis and tissue differentiation. To measure these forces, we developed a new Förster resonance energy transfer (FRET)-based tension sensor that uses the actin-associated protein, Lima1. The sensor was validated in HeLa cells where we found the FRET index decreased or increased in response to changes in the cellular environment. Introducing the sensor into Xenopus embryos enabled us to observe tension distributions and sequential changes over the entire embryo. We found that during neural tube closure, neural ectodermal cells showed a gradual decrease in their FRET index, indicating they generate higher tension with the progression of neural tube closure. With appropriate controls and application, our Lima1 tension sensor has the ability to uncover and define other tension distributions and their functions in development and differentiation.