Cellular and Molecular Events During Cytokinesis
The molecular events dictating cellular division require the orchestration of numerous signaling and actin cytoskeleton interacting proteins. The cleavage furrow is the site of actin, actin-interacting proteins, septins and microtubule assembly into a contractile ring, and is regulated by numerous signaling proteins, such as Rho. Coordination of this cellular machinery results in the eventual formation of two separate and fully functioning daughter cells.
The mitotic spindle and the cleavage furrow are intimately linked, with furrow placement dictated by the position of the metaphase plate. As a consequence when the mitotic spindle is in the center of the cell, a symmetrical cleavage furrow is formed around the periphery of the ell, the so-called purse string arrangement. When the spindle is asymmetrically positioned in a cell, the furrow is displaced from the cell equator producing daughter cells of unequal size. In some large eggs, when a small spindle lies parallel to the membrane at one side of the cell the resultant cleavage furrow forms at that side over the former metaphase plate, and as it contracts, the furrow propagates around the equator of the cell. In tissue culture cells when the spindle is positioned asymmetrically, actin and myosin assemble over the former metaphase plate in an asymmetric pattern and contraction is asymmetric, beginning at the side of the cell closest to the spindle.
The correlation of cleavage furrow position with metaphase plate position becomes more complicated when multiple spindles are present in one cell. Previous experiments demonstartated when manipulating an echinoderm zygote to form a doughnut or torus containing two mitotic spindles, cleavage furrows formed not only around the center of each spindle, but could also form between the centrosomes of the adjacent spindles. Other experiments showed that if a centrally positioned spindle was made smaller, it did not induce the formation of a cleavage furrow unles it was moved closer to the cell surface. We have performed microinjection studies and monitored the activity of numerous live fluorescently labeled probes to address protein incorporation during cytokinesis. These types of experiments address not only if a furrow formed, but when and where the contractile cytoskeletal proteins first appeared in the furrow region after the initiation of anaphase. We have found that cleavage furrows form not only between separating daughter chromosomes but also between controsomes of adjacent spindles. We have also shown that contractile proteins appear in the future cleavage furrows before any sign of surface contractions. These experiments support the hypothesis that the mechanism for the establishment of cleavage furrows is the same for all types of cells and that the centrosomes and their linearly connected microtubules may play an important role for the assembly of the cleavage furrow.