Telophase correction refines division orientation in stratified epithelia

Abstract

ABSTRACTDuring organogenesis, precise control of spindle orientation ensures a proper balance of proliferation and differentiation. In the developing murine epidermis, planar and perpendicular divisions yield symmetric and asymmetric fate outcomes, respectively. Classically, division axis specification involves centrosome migration and spindle rotation, events that occur early in mitosis. Here, we identify a previously uncharacterized orientation mechanism that occurs during telophase, correcting erroneous oblique orientations that unexpectedly persist into anaphase. The directionality of reorientation—towards either planar or perpendicular—correlates with the maintenance or loss of basal contact by the apical daughter. While the conserved scaffolding protein Pins/LGN is believed to function primarily through initial spindle positioning, we now show it also functions actively during telophase to reorient oblique divisions toward perpendicular. The ability to undergo telophase correction is also critically dependent upon an LGN-independent pathway involving the tension-sensitive adherens junction proteins vinculin, a-catenin and afadin, and correction directionality is influenced by local cell density. Failure of this reorientation mechanism impacts tissue architecture, as excessive oblique divisions induce precocious differentiation. The division orientation plasticity provided by telophase correction may provide a means for progenitors to dynamically respond to extrinsic cues provided by neighboring cells in order to adapt to local tissue needs.