Telophase correction refines division orientation in stratified epithelia

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.

Three-dimensional geometry controls division symmetry in stem cell colonies

“…However, for cells where only one prospective daughter cell displays substantial contact with the colony, the spindle displays high mobility and divisions are asymmetric in size ( Figs 1 – 3 ). E-cadherin has been implicated in orienting cell division along the epithelial plane in several mammalian epithelia ( den Elzen et al, 2009 ; Lázaro-Diéguez and Müsch, 2017 ; Lough et al, 2019 ). For instance, in the skin epidermis, cell–cell adhesions have been shown to play a role in refining the position of the spindle at the end of mitosis, independently of the spindle positioning protein LGN ( Lough et al, 2019 ), while E-cadherin directs spindle orientation through LGN in prostate epithelia ( Wang et al, 2018 ).…”

“…E-cadherin has been implicated in orienting cell division along the epithelial plane in several mammalian epithelia ( den Elzen et al, 2009 ; Lázaro-Diéguez and Müsch, 2017 ; Lough et al, 2019 ). For instance, in the skin epidermis, cell–cell adhesions have been shown to play a role in refining the position of the spindle at the end of mitosis, independently of the spindle positioning protein LGN ( Lough et al, 2019 ), while E-cadherin directs spindle orientation through LGN in prostate epithelia ( Wang et al, 2018 ). It will be interesting in the future to investigate the mechanistic link between spindle positioning and E-cadherin in ESCs.…”

The crosstalk between microtubules, actin and membranes shapes cell division

“…We recently reported that in metaphase HeLa cells, the actin-binding protein, Afadin, controls spindle orientation by binding concomitantly to LGN and to cortical F-actin [47]. Recent data from the Williams laboratory confirmed that in murine developing skin Afadin is implicated in setting vertical and planar divisions in anaphase [48].…”

Going with the flow: insights fromCaenorhabditis eleganszygote polarization

“…Cell divisions are subsequently oriented relative to cell contacts in the developing embryo [244]. Given that actomyosin contractility/flow affects centrosome separation/orientation in a wide range of biological contexts [108,[243][244][245][246][247][248], it is key to understand how these seemingly divergent processes are coupled.…”

“…(Sugioka 2018). Given that actomyosin contractility/flow affect centrosome separation/orientation in a wide range of biological contexts[108,[242][243][244][245][246][247]] (Rosenblatt 2004, Sommi 2011, Naganathan 2014, Lazaro-Dieguez, Musch 2017, Scarpa 2018, Sugioka 2018, Lough 2019) it is key to understand how these seemingly divergent processes are coupled.…”