Telophase correction refines division orientation in stratified epithelia

Elife. 2019 Dec 13;8:e49249. doi: 10.7554/eLife.49249.

Abstract

During organogenesis, precise control of spindle orientation balances 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 occurring early in mitosis. Here, we identify a novel orientation mechanism which corrects erroneous anaphase orientations during telophase. The directionality of reorientation correlates with the maintenance or loss of basal contact by the apical daughter. While the scaffolding protein LGN is known to determine initial spindle positioning, we show that LGN also functions during telophase to reorient oblique divisions toward perpendicular. The fidelity of telophase correction also relies on the tension-sensitive adherens junction proteins vinculin, α-E-catenin, and afadin. Failure of this corrective mechanism impacts tissue architecture, as persistent oblique divisions induce precocious, sustained differentiation. The division orientation plasticity provided by telophase correction may enable progenitors to adapt to local tissue needs.

Keywords: adherens junction; asymmetric cell division; cell biology; cell-cell adhesion; developmental biology; epidermal differentiation; mouse; oriented cell division; spindle orientation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Actomyosin / physiology
  • Anaphase
  • Animals
  • Cell Self Renewal
  • Cell Shape
  • Cytoskeleton / ultrastructure
  • Epidermal Cells / cytology*
  • Epidermis / embryology
  • Epithelial Cells / cytology*
  • Female
  • Genes, Reporter
  • Intravital Microscopy
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microfilament Proteins / deficiency
  • Microfilament Proteins / genetics
  • Microfilament Proteins / physiology
  • Protein Conformation
  • RNA Interference
  • Spindle Apparatus / ultrastructure
  • Telophase / physiology*
  • Vinculin / genetics
  • Vinculin / physiology
  • alpha Catenin / genetics
  • alpha Catenin / physiology

Substances

  • Ctnna1 protein, mouse
  • Microfilament Proteins
  • Vcl protein, mouse
  • afadin
  • alpha Catenin
  • Vinculin
  • Actomyosin