A narrow window of cortical tension guides asymmetric spindle positioning in the mouse oocyte

Abstract

Cell mechanics control the outcome of cell division. In mitosis, external forces applied on a stiff cortex direct spindle orientation and morphogenesis. During oocyte meiosis on the contrary, spindle positioning depends on cortex softening. How changes in cortical organization induce cortex softening has not yet been addressed. Furthermore, the range of tension that allows spindle migration remains unknown. Here, using artificial manipulation of mouse oocyte cortex as well as theoretical modelling, we show that cortical tension has to be tightly regulated to allow off-center spindle positioning: a too low or too high cortical tension both lead to unsuccessful spindle migration. We demonstrate that the decrease in cortical tension required for spindle positioning is fine-tuned by a branched F-actin network that triggers the delocalization of myosin-II from the cortex, which sheds new light on the interplay between actin network architecture and cortex tension.

The blood vessels development, morphogenesis and blood circulation are three ontologic groups highly up-regulated in porcine oocytes before in vitro maturation

“…Smooth muscle aortic alpha-actin (ACTA2) seems to play an important role in this process. During oocyte maturation actin cytoskeleton participates in the formation of the cortical actin cap, increasing the cytoplasmic actin density [23] and the thickness of cortical actin [24]. The actin cytoskeleton is the main driving force for asymmetric division in mammalian oocytes.…”

Roles of actin binding proteins in mammalian oocyte maturation and beyond

“…In addition to the small GTPase pathway, the actin polymerization pathway may be connected with well-known signaling pathways governing the cell cycle, including the MPF or Mos-MAP kinase pathways, and elucidation of these mechanisms could be critical for increasing our understanding of the regulation of ARP2/3-mediated actin polymerization based on cell cycle progression. Recent studies 12,13 show that WAVE2 is phosphorylated by the extracellular signalregulated kinase (ERK) pathway and activates ARP2/3-dependent actin polymerization as oocyte maturation progresses in mice, demonstrating the presence of crosstalk between the 2 signaling pathways. It is also possible that other NPFs and ABPs are regulated by MPF or MAPK pathways during oocyte maturation; however, the details of these mechanisms have not yet been elucidated.…”

“…84 The moment of exclusion of tropomyosin from the cortex during oocyte maturation coincides with the exclusion of non-muscle myosin II, 12 which is directly related to cortex softening, a driving force for asymmetric spindle migration. 12,13,35,89 It is unclear whether exclusion of tropomyosin from the cortex is the consequence or cause of myosin II exclusion, and the relationship between these proteins needs to be clarified. However, based on the functional roles of tropomyosin in the regulation of myosin-actin interactions, 90-93 the exclusion of tropomyosin could directly facilitate the exclusion of myosin II.…”

“…23 Moreover, the ARP2/3 complex is responsible for the formation of a thicker cortex region called the 'subcortex'; the formation of the subcortex by ARP2/3 may be a factor mediating the exclusion of non-muscle myosin II and can cause changes in cortex softening during oocyte maturation. 12,13 Nucleation-promoting factor (NPF) family proteins are necessary for the activation of the ARP2/3 complex, and several NPFs, including Wiskott-Aldrich syndrome protein family member 2 (WAVE2), 66 neuronal Wiskott-Aldrich syndrome protein (N-WASP), 67 junction-mediated regulatory protein (JMY), 68 WASP homolog associated with actin, membranes, and microtubules (WHAMM), 69 and WAS protein family homolog 1 (WASH), 70 are implicated in oocyte maturation (Fig. 2D).…”

“…[5][6][7][8][9] One of the most dramatic changes in the actin cytoskeleton during mammalian oocyte maturation is the formation of the cortical actin cap near the migrating spindle. 5 In addition to actin cap formation, cytoplasmic actin density 10,11 and the thickness of cortical actin 12,13 increases during oocyte maturation ( Fig. 1).…”