RT Journal Article
SR Electronic
T1 Telophase correction refines division orientation in stratified epithelia
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 668244
DO 10.1101/668244
A1 Kendall J. Lough
A1 Kevin M. Byrd
A1 Carlos P. Descovich
A1 Danielle C. Spitzer
A1 Abby J. Bergman
A1 Gerard M. Beaudoin III
A1 Louis F. Reichardt
A1 Scott E. Williams
YR 2019
UL http://biorxiv.org/content/early/2019/06/13/668244.abstract
AB During 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.