Nuclear movement in multinucleated cells

Abstract

Nuclear movement is crucial for the development of many cell types and organisms. Nuclear movement is highly conserved, indicating its necessity for cellular function and development. In addition to mononucleated cells, there are several examples of cells in which multiple nuclei exist within a shared cytoplasm. These multinucleated cells and syncytia have important functions for development and homeostasis. Here, we review a subset of the developmental contexts in which the regulation of the movement and positioning of multiple nuclei are well understood, including pronuclear migration, the Drosophila syncytial blastoderm, the Caenorhabditis elegans hypodermis, skeletal muscle and filamentous fungi. We apply the principles learned from these models to other systems.

Keywords: Cytoskeleton; LINC complex; Nuclear movement; Syncytia.

Fig. 1.

Pronuclear movement. (A) Cargo-transport mechanism of nuclear movement in C. elegans. The female pronucleus is coated with dynein, which interacts with microtubules that extend from the sperm aster that is associated with the male pronucleus. Dynein then travels toward the minus-ends of the microtubules carrying the female pronucleus. (B) Microtubule pushing mechanism in sea urchin. The microtubule aster associated with the male pronucleus grows into and pushes against the cortex (indicated by arrows) of the cell to propel the male pronucleus toward the center, independent of its interactions with the female pronucleus.

Fig. 2.

Cytoplasmic mixing in the early stages of Drosophila blastoderm development. An early stage Drosophila syncytial blastoderm. A band of actin-myosin contractility near the center of the developing blastoderm creates cytoplasmic mixing that redistributes the nuclei based on dispersion physics. Left inset shows the contraction of the actin-myosin network that provides the force to mix the cytoplasm, whereas the right inset shows the relaxation of the actin-myosin network that correlates with stationary nuclei.

Fig. 3.

Microtubule sliding in the Drosophila blastoderm. A late Drosophila syncytial blastoderm in which spindles are near enough to their neighbors that they interact. Mitotic spindles associate with their neighbors through their astral microtubules. Insets show kinesin localized to the regions of overlapping antiparallel microtubules. The inset at the top shows the organization in the Drosophila blastoderm in which Feo1 cooperates with kinesin to link and slide the antiparallel microtubules. The inset to the bottom shows an example where a bipolar kinesin can slide the antiparallel microtubules in the absence of another factor.

Fig. 4.

Nuclear movement in muscle. This is a general model based on data from cultured myotubes and in vivo Drosophila muscles. (A) The microtubules associated with a newly incorporated nucleus associate with the microtubules from the already incorporated nuclei in the center of the muscle. (Aa) Hypothetically, a minus-end directed motor could interact with the overlapping antiparallel microtubules and slide these microtubules to move nuclei together. (Ab) Dynein localized to the nuclear envelope carries the newly incorporated nucleus toward the already incorporated nuclei. Crucially, when the active motor is kinesin, the cargo-transport model moves nuclei away from their neighbors. (B) Nuclei are spaced equidistantly from their neighbors. Two mechanisms have been proposed. (Ba) Kinesin-dependent sliding of antiparallel microtubules moves nuclei away. (Bb) Dynein-dependent cortical pulling moves nuclei away from the cluster. (C) Nuclei move to the periphery of the muscle when myofibrils are zippered together in a desmin-dependent mechanism. The density of the myofibril network excludes the large nucleus from the cell interior.

Fig. 5.

Cortical pulling as seen in Ashbya gossypii. Microtubules extend from the microtubule-organizing center that is associated with a nucleus and interact with dynein that is anchored at the cortex. Because dynein is anchored and cannot move, it pulls the minus-end of the microtubule toward its position.