Jasplakinolide application to the equatorial region, which stabilizes actin filaments, abolished cleavage furrow ingression, whereas its polar application had no effect on furrow ingression. In contrast, cytochalasin D application around the equatorial region, which disrupts actin filaments, facilitated furrow ingression. Importantly, cytochalasin D application to the polar region abolished furrow ingression. From these results, the ‘‘equatorial collapse model’’ was proposed in which the cell surface should be relatively soft around the equatorial region compared to the polar regions for the furrow to ingress. The molecular mechanism for softening may involve the regulation of the small GTPase Rac, the activation of which leads to the formation of actin meshwork structures. A fluorescence resonance energy transfer study in mammalian cells demonstrated that Rac is locally inactivated around the cell equator. A genetic study in Caenorhabditis elegans suggested that Rac is inactivated by the conserved cytokinesis regulator centralspindlin, and this regulation is essential for furrow ingression. Centralspindlin is a heterotetrameric complex composed of two molecules of kinesin6, MKLP1-ZEN-4, and two molecules of MgcRacGAP-CYK-4, Lomitapide Mesylate which contains a GTPase-activating protein domain for Rho family GTPases. One possibility suggested by these data is that centralspindlin promotes cytokinesis by locally reducing cortical stiffness at the cell equator. To date, there is relatively little experimental information on cortical stiffness during cytokinesis. Measurements with atomic force microscopy indicated that the equatorial region was stiffer than the other regions. However, this may not contradict the equatorial softening model because the AFM measurements of equatorial stiffness would likely include the high contractility of the contractile ring in addition to cell surface stiffness. To investigate cell surface stiffness alone, we developed a means to compute cell surface stiffness from in vivo cell shapes using a theoretical model based on cortical bending stiffness. Our analysis indicates that the stiffness of the equatorial cell surface is Lesinurad reduced during cytokinesis and that this reduction depends on the centralspindlin component ZEN-4. We also show theoretical predictions for the relative contribution of softening and the contractile ring to furrow ingression. To examine whether cell surface stiffness is reduced around the cleavage furrow, we estimated spatio-temporal changes in surface stiffness by fitting in vivo cell shapes to a mathematical model. In principle, if we have a mathematical model that allows us to calculate cell shapes under given cell surface stiffness, then conversely, we could predict surface stiffness by using in vivo cell shapes. This strategy is similar to that used to predict cell surface tension in sea urchin eggs. We defined 1 unit length as 14.5 mm, which corresponds to the radius at the furrow region before ingression. As the furrow ingressed, the cell surface area increased, whereas the cell volume was almost constant. We used these measured values for shape calculation with our mathematical model. The curvatures along the meridians and along the parallels of latitude were nearly uniform in the initial phase of cytokinesis. In contrast, Cm was very low around the equatorial region in the final phase, which generates a steep concavity corresponding to the furrow. A noteworthy feature was that Cm was not constant even in the outer region of the furrow, but was slightly larger around the region neighboring the furrow, s=0.6–0.8, strongly suggesting that cell surface stiffness is not spatially constant. What is the molecular regulator of the equatorial reduction in cell surface stiffness? Centralspindlin is a molecular complex essential for furrow ingression: in the C. elegans embryo, mutation or depletion of centralspindlin components causes the arrest of furrow ingression at approximately the half-way point of closure.