Asymmetric centrosome behavior and the mechanisms of stem cell division

Abstract

The ability of dividing cells to produce daughters with different fates is an important developmental mechanism conserved from bacteria to fungi, plants, and metazoan animals. Asymmetric outcomes of a cell division can be specified by two general mechanisms: asymmetric segregation of intrinsic fate determinants or asymmetric placement of daughter cells into microenvironments that provide extrinsic signals that direct cells to different states. For both, spindle orientation must be coordinated with the localization of intrinsic determinants or source of extrinsic signals to achieve the proper asymmetric outcome. Recent work on spindle orientation in Drosophila melanogaster male germline stem cells and neuroblasts has brought into sharp focus the key role of differential centrosome behavior in developmentally programmed asymmetric division (for reviews see Cabernard, C., and C.Q. Doe. 2007. Curr. Biol. 17:R465-R467; Gonzalez, C. 2007. Nat. Rev. Genet. 8:462-472). These findings provide new insights and suggest intriguing new models for how cells coordinate spindle orientation with their cellular microenvironment to regulate and direct cell fate decisions within tissues.

Figure 1.

Asymmetric centrosome/SPB behavior during asymmetric cell divisions. (A) Structure of the stem cell niche in the Drosophila male germline. Somatic hub cells are the major components of the niche for male GSCs. The GSC attaches to the hub via adherens junction (red lines) so that it can receive the signaling ligand, Upd, from the hub (yellow allow) to activate the JAK–STAT (Janus kinase–signal transducer and activator of transcription) pathway. The stem cell daughter that is displaced away from the hub (gonialblast; GB) starts differentiation. (B) Consistent centrosome positioning orients the mitotic spindle in male GSCs. The mother centrosome (red dots) is always located close to the hub, whereas the daughter (yellow dots) migrates toward the opposite side of the cell to set up orientation of the mitotic spindle. (C) Asymmetric division of the Drosophila neuroblast (NB). The neuroblast divides asymmetrically by segregating fate determinants. Apical protein complexes (red lines) include Par6, Baz, and atypical PKC, and basal fate determinants (blue lines) include Numb, Miranda, and Prospero (for a more comprehensive set of asymmetrically localized proteins, see the review Yu et al., 2006). (D) Consistent centrosome behavior orients the mitotic spindle in the neuroblast. The apical centrosome (large red dots) retains MTOC activity throughout the cell cycle, whereas the other centrosome (small red dots) becomes active only at the G2-M transition. The inactive centrosome migrates toward the basal side during interphase. Pins might be functioning to provide a cortical cue to anchor active MTOC. (E) Spindle orientation in budding yeast. The mother SPB is normally delivered to the bud cell, where it is captured by the bud tip cortex. This process is mediated by astral microtubules emanating from the mother SPB and Kar9 protein. Cell cycle regulators such as Tem1 and Bub2/Bfa1 are specifically localized to the bud-directed SPB (normally the mother SPB) to coordinate spindle position and cell cycle progression.