141 Oral - Patterning and Morphogenesis I
Saturday April 09, 9:15 AM - 9:30 AM

Authors:
Jaclyn Camuglia ¹; Soline Chanet ²; Adam Martin ¹

Affiliations:
1) Massachusetts Institute of Technology; 2) Collège de France

Keywords:
w. biomechanical forces; f. spindles and motors

Epithelial morphogenesis and homeostasis are properly achieved by oriented cell divisions that occur along specific directions relative to both the epithelial plane and the polarity of an organ/organism. In epithelial sheets of cells, divisions can occur either perpendicular or parallel (planar) to epithelial sheets. Planar cell divisions can further exhibit polarity in specific orientations along epithelial tissues (planar polarization). Spindle orientation is often achieved by a complex of Pins/LGN, Mud/NuMa, Gai, and Dynein, which interacts with astral microtubules to rotate the spindle. Here, we identify the mitotic domains of the early embryo as a system to study Pins-mediated planar polarized divisions during morphogenesis. Mitotic domains (MDs), 1, 3, 5, and 14 exhibit oriented division and these oriented divisions are dependent on proper Pins localization and activity. We find that the divisions within these domains are oriented within 30 degrees of the anterior-posterior (AP) axis of the embryo and that Pins is localized in planar polarized crescents within the domains. Disruption of Pins localization and activity via expression of a myristoylated version of Pins leads to misoriented divisions. It is currently unknown what causes Pins localization in this context. Both planar polarity proteins and mechanical force have been shown to localize Pins and cue spindle orientation during division. We find that in MDs 1, 3, 5, and 14 canonical planar cell polarity pathways are not solely responsible for the orientation of the divisions. Further, we find that adherens junctions, which mechanically couple cells within epithelia, are necessary for the orientation of the divisions. Disruption of a-catenin disrupts division orientation and pins polarization. Our findings suggest mechanical forces, specifically those generated during morphogenesis are responsible for Pins polarization and spindle orientation. Disruption of forces through a chemical inhibitor, laser ablation, and genetic perturbation causes divisions to fail to orient along the AP axis and abolishes Pins polarization. To our knowledge, demonstrating that mechanical force polarizes Pins to mediate division orientation has not yet been shown in vivo.