Symmetry breaking in hydrodynamic forces drives meiotic spindle rotation in mammalian oocytes

Abstract

Patterned cell divisions require a precisely oriented spindle that segregates chromosomes and determines the cytokinetic plane. In this study, we investigated how the meiotic spindle orients through an obligatory rotation during meiotic division in mouse oocytes. We show that spindle rotation occurs at the completion of chromosome segregation, whereby the separated chromosome clusters each define a cortical actomyosin domain that produces cytoplasmic streaming, resulting in hydrodynamic forces on the spindle. These forces are initially balanced but become unbalanced to drive spindle rotation. This force imbalance is associated with spontaneous symmetry breaking in the distribution of the Arp2/3 complex and myosin-II on the cortex, brought about by feedback loops comprising Ran guanosine triphosphatase signaling, Arp2/3 complex activity, and myosin-II contractility. The torque produced by the unbalanced hydrodynamic forces, coupled with a pivot point at the spindle midzone cortical contract, constitutes a unique mechanical system for meiotic spindle rotation.

RhoA- and Cdc42-induced antagonistic forces underlie symmetry breaking and spindle rotation in mouse oocytes

“…While evidence suggests that spindle rotation is prevented by actin depolymerization, myosin II inhibition or RhoA inactivation [29][30][31], the underpinnings of this unique symmetry breaking event have long remained elusive. In a recent study, Wang and colleagues provided new insights into this mechanism, showing that rotation is achieved through an asymmetric distribution of forces along the anaphase II spindle [32]. It was suggested that spindle rotation arises from cytoplasmic flows of opposite directions at the 2 ends of the spindle, consecutive to spontaneous symmetry breaking in the distribution of Arp2/3 and myosin-II at the cortex [32].…”

Epidermal growth factor receptor signaling uncouples germ cells from the somatic follicular compartment at ovulation

“…To test this idea, we treated COCs with EGF for 8 h in the absence or presence of the canonical inhibitor of Arp2/3-mediated actin assembly, CK666, which acts by stabilizing the inactive form of the complex 62 and has previously been used to inhibit Arp2/3 in oocytes 43 , 63 . We found that the TZPs detached from the oocyte under these conditions, as indicated by the visible gap between the tips of the TZPs and the oocyte surface marked by phalloidin staining (Fig.…”

A Critical Role for The COP9 Signalosome Subunit 3 as A Gatekeeper of Genome Integrity in 2-Cell Mouse Embryos

“…Together, these two answers predict that a complete depletion by TRIM21-mediated proteasomal degradation may not work, and may not be required to work (depending on one's aim), for every protein. Indeed, it may be noted that out of thirteen studies which applied the TRIM21-mediated proteasomal degradation on oocytic or embryonic proteins in mammals 21,22,27,[65][66][67][68][69][70][71][72][73][74] , four studies reported complete depletion (ITPR1 67 ; SNAP23 27 ; G6PD, PKM, GFPT1 65 ; EG5 also known as KIF11 21 ), four studies reported almost complete depletion (BTG4 68 ; TACC3 69 ; RACGAP1 also known as CYK4 and PLK1 70 ; SMC3 72 ) and five studies reported incomplete depletion (RCC1 66 ; CENPF 71 ; TEAD4 22 ; aPKC also known as PRKC 73 ; HUWE1 74 ). Thus, complete removal of the protein of interest seems to be more the exception than the rule (with current technology).…”