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.
Highlights
Stem and progenitor cells utilize asymmetric cell divisions to balance self-renewal and differentiation
We demonstrate that the α-catenin/vinculin/afadin cytoskeletal scaffolding complex is required for this correction to occur, and likely functions to modulate the tensile properties of the cell cortex by altering how actin is recruited to adherens junctions (AJs)
While previous studies have demonstrated essential roles for canonical spindle orientation genes in division orientation, we show that initial spindle positioning is only one part of the process
Summary
Stem and progenitor cells utilize asymmetric cell divisions to balance self-renewal and differentiation. Basal progenitors are capable of dividing either within the plane of the epithelium or perpendicular to it, resulting in symmetric or asymmetric divisions, respectively (Lechler & Fuchs, 2005; Smart, 1970). This process is governed by a conserved complex of spindle orienting proteins, including the essential linker LGN/Gpsm (Williams, Beronja, Pasolli, & Fuchs, 2011; Williams, Ratliff, Postiglione, Knoblich, & Fuchs, 2014). A parsimonious explanation for the observed bimodal distribution of division angles is that perpendicular divisions occur when sufficient levels of LGN are recruited to the apical cortex during early mitosis, and planar divisions occur when this apical recruitment fails
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