Spindle assembly: asters part their separate ways

PERSPECTIVESpindle assembly: asters part their separate waysJody RosenblattCells have developed diverse ways to separate two microtubule asters to form a mitotic spindle. Here, I focus on two mechanisms

used to position asters around chromosomes during mitosis: first, aster migration around the nuclear envelope and, second, aster

attachment to a contractile cortex at the plasma membrane after the nuclear envelope has broken down. Although certain cell

types use one mechanism predominantly, most rely on both to ensure proper spindle assembly.To guarantee that a cells entire genome is faithfully transmitted, chromosomes duplicate, condense, and segregate on a mitotic spindle. The

mitotic spindle consists of two microtubule

asters that span either side of the condensed

chromosomes. During prophase, when the

spindle starts to assemble, the centrosomes

that nucleate asters separate around the nuclear

envelope (Fig. 1a). After the nuclear envelope

has broken down (NEBD) during prometaphase, the asters continue to separate until

they become aligned on either side of the condensed chromosomes (Fig. 1b). Once the asters

have completed migration, some of the aster

microtubules will bind to the chromosomes

and align them at the metaphase plate.For a spindle to assemble correctly, the centrosomes must migrate in the correct direction and stop migrating once they reach their

appropriate location on either side of the chromosomes. Moreover, in most cases the spindle

must position itself centrally within a cell so

that the two daughter cells produced are of the

same size and composition. Even in cases in

which a cell is programmed to divide asymmetrically, it first forms a spindle that fits symmetrically in a cell and then rotates or shifts

the spindle to make the asymmetric division

(for an example, see ref. 1). Therefore, spindle

assembly must be considered in conjunction

with spindle positioning within the cell.Although the spindle was discovered over

120 years ago (see ref. 2 for a review), we still

know surprisingly little about the processes

that drive its assembly. Although genetics

and cytological analyses of fixed and live cells

have greatly increased our knowledge of how

a spindle assembles, much recent progress has

come from in vitro spindle self-assembly assays.

However, it is important to note that the spindles that were assembled in these in vitro assays

use an alternative pathway that is typical...