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Fig. 6.3 Asymmetric centrosome segregation and inheritance during asymmetric stem cell
division. a Drosophila germline stem cells divide asymmetrically and the mother centrosome is
inherited by the stem cell daughter. At the center of the stem cell niche, hub cells produce
external fate determinants within the niche. The mother centrosome (black) locates close to the
stem cell-hub interface while the daughter centrosome (red) is mostly found to be at the basal
side. During mitosis, germline stem cells form stable and stereotypical oriented mitotic spindles
with mother/daughter centrosome asymmetrically positioned. After cell division, one daughter
cell receiving the mother centrosome maintains contact with the hub cell and retains self-renewal
ability. The other daughter cell receiving the daughter centrosome is displaced away from the hub
and starts differentiation. b Radial glial progenitors in the ventricular zone of the mouse neocortex
divide asymmetrically, and the self-renewing daughter inherits the mother centrosome (black).
The centrosome in radial glial progenitor locates very close to the ventricular zone. Upon cell
division, a mitotic spindle with asymmetric centrosomes forms at the surface of the ventricular
zone. Therefore, the self-renewing radial glial progenitor inherits the mother centrosome, while
the daughter centrosome is received by the differentiating cell. c Drosophila neuroblasts divide
asymmetrically, but the daughter centrosome is received by the self-renewing daughter while the
mother centrosome is retained by the differentiating daughter. Intrinsic self-renewal fate
determinants, such as Par and Pins complexes, form a crescent (brown) and localize at the apical
end; and differentiation-promoting proteins, such as Numb/Pros/Brat/Miranda complex, form the
basal crescent (yellow). Upon cell division, the daughter centrosome (red) locates near the apical
crescent and the mother centrosome (black) positions near the basal crescent. Therefore, this
spindle positioning leads to asymmetric segregation of centrosomes and intrinsic fate
determinants, producing one self-renewing neuroblast in a larger size with the daughter
centrosome and one differentiating ganglion mother cell in a smaller size with the mother
centrosome
b
process, formation of a bipolar spindle in a cell containing more than two centro-
somes, requires a functional spindle assembly checkpoint, which inhibits the ana-
phase-promoting complex, and thus delays mitotic exit. This study showed that
centrosome overamplification does not necessarily lead to multipolar cell division,
leading to genomic instability, as has been suggested as a possible underlying
mechanism that explains frequent centrosome overamplification in cancer cells.
Interestingly, however, an unusually high percentage of NBs undergo symmetric
division upon overamplification of centrosomes (Basto et al.
2008
).
Almost a century ago, abnormalities in centrosome number were hypothesized
to result in chromosomal alternations due to a failure in equal partitioning of the
genome, triggering cancer development. This seemed to fit well with the obser-
vation that many cancer cells often show centrosome overamplification. Multiple
lines of evidence have since shown that genetic alterations and instability are
involved in tumor development and cancer, but the causative relationship between
centrosome abnormalities and genetic alterations in cancer development remained
elusive. A recent study provided the first critical evidence that genomic instability
might not be the reason for tumor formation upon centrosome dysfunction
(Castellanos et al.
2008
). The authors systematically examined the tumor-forming
ability of cells derived from fly brain upon transplantation to a host fly abdomen.
Cells defective in centrosome function (such as mutants of dsas-4, polo or aurA)
resulted in tumor formation, but without significant changes in the cellular DNA
content. Instead, these cells with defective centrosomes showed a failure in
asymmetric NB division. Critically, cells defective in genome stability (such as
