Schrock, D. | Search bioRxiv

bioRxiv2026

A myosin filament cage drives multiple aspects of mitosis unique to cells dividing within a polarized epithelium

Here we used mouse intestinal organoids expressing endogenously tagged myosin to clarify its roles in those aspects of mitosis unique to division within a polarized epithelium. Super-resolution imaging of rounded metaphase cells revealed a never-before-seen myosin filament cage that only forms in this context, exhibits apical/basal polarity, maintains roundness by resisting surrounding tissue pressure, and repositions laterally to form a contractile ring predetermined to drive planar division and asymmetric cleavage furrow progression. Attenuating cage function inhibited interkinetic nuclear migration and metaphase cell rounding, causing the division plane to shift from planar to orthogonal and resulting in organoids possessing multiple lumens. Following the apical domain marker ZO-1 showed that the new lumens originate at the interface between stacked daughter cells created by orthogonal divisions. We conclude that cells dividing within polarized epithelia create a myosin filament cage designed specifically to drive those aspects of cell division unique to their context.

cell biology↗

bioRxiv2026

Myo10-dependent leading-edge coordination maintains physical coherence of migrating dendritic cells

Dendritic cells (DCs) are the principal leukocytes responsible for priming T cells. DC migration though geometrically complex tissue environments is crucial for initiating robust and spatiotemporally coordinated activation of adaptive immune responses. However, our understanding of the molecular mechanisms that govern physical navigation of DCs remains incomplete. Here we identify the unconventional myosin Myo10 as a critical regulator of DC trafficking. We show that loss of Myo10 attenuates FITC-induced contact hypersensitivity and reduces the efficiency of in vivo DC migration and egress from dermal explants but notably has no effect on antigen uptake or in vitro T cell priming. We further find that the migration defects of Myo10-deficient cells are exacerbated by increasing geometrical complexity. Mechanistically, Myo10 promotes physical coherence and coordinated leading edge dynamics via its interaction with lamellipodin, which subsequently drives VASP-mediated actin polymerization. Together, our findings establish a vital Myo10-lamellipodin-VASP axis essential for spatiotemporal DC navigation through restrictive microenvironments, providing critical insights into the biophysical regulation of immune surveillance.

cell biology↗