Biology Reference
In-Depth Information
(Yamashita et al.
2007
). Electron micrographs showed that there are indeed more
astral microtubules around the mother centrosome than the daughter centrosome in
wild type GSCs, presumably explaining the asymmetrical positioning and motility of
the mother/daughter centrosomes. Furthermore, centrosome separation in GSCs
occurs unusually early, suggesting that GSCs could take advantage of the difference
in motility and/or stability of mother versus daughter centrosomes to position the
daughter centrosome at the basal side of the cell, thus ensuring asymmetric stem cell
division, and thus their asymmetric inheritance. Similarly, in the mammalian neo-
cortex, the mother centrosome is preferentially inherited by the neural progenitor cell
while the daughter centrosome is largely associated with the differentiating neuron
(Wang et al.
2009
). Strikingly, this centrosome asymmetry is closely related to the
stem cell fate and maintenance. In the event of RNAi knockdown of ninein, a
component of subdistal appendages in the mature centrosome, this asymmetric
centrosome inheritance is disrupted, resulting in the depletion of the neural pro-
genitors (Fig.
6.3
b).
Another interesting example is found in Drosophila NBs. NBs undergo
asymmetric stem cell division, generating two daughter cells with unequal sizes.
During mitosis, spindle orientation is critical and must be in line with the polarity
axis of the NB to ensure an asymmetric division (Rebollo et al.
2007
; Rusan and
Peifer
2007
); pulling forces acting on the astral MTs work to determine the
position of the mitotic spindle and are responsible for the differences in NB
daughter cell sizes (Neumuller and Knoblich
2009
). However, contrary to the
centrosome inheritance in fly GSCs and mammalian neural progenitors, the
daughter centrosome is consistently retained by the stem cell while the mother
centrosome is inherited by the GMC (Conduit and Raff
2010
; Januschke et al.
2011
). To achieve this, Cnn is downregulated in the mother centrosome and the
MTOC activity of the mother centrosome is reduced, while the level of Cnn is
maintained in the daughter centrosome and the daughter centrosome functions as
MTOC every cell cycle (Conduit and Raff
2010
). Instead of relying on the passive
maintenance of the MTOC, fly NBs utilize this elaborate mechanism of actively
regulating the MTOC of each centrosome every cell cycle to achieve asymmetric
centrosome segregation and inheritance, implying that NBs do have a reason to do
so, although such a reason has yet to be elucidated (Fig.
6.3
c).
The asymmetric centrosome segregation and inheritance during asymmetric stem
cell divisions implies that stem cells do have reason(s) to inherit one particular
centrosome over the other, provoking further studies to understand the biological
meaning of this phenomenon. One possible explanation is that the mother/daughter
centrosomes asymmetrically harbor fate determinants, so that the daughter cell
inheriting the ''stemness''-promoting centrosome remains as the stem cell, while the
other daughter cell receiving the ''differentiation''-initiating centrosome differenti-
ates. For example, in mollusc embryos, certain mRNAs asymmetrically associated
with the centrosome are asymmetrically distributed during division, producing two
daughter cells with asymmetric fates (Lambert and Nagy
2002
).
