Wellcome/Cancer Research UK Institute and Department of Genetics,
University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK
* Present address: HHMI, Department of Biochemistry and Molecular Biophysics,
Center for Neurobiology and Behavior, Columbia University, 701 West 168th
Street, New York, NY 10032, USA
Author for correspondence (e-mail:
ahb{at}mole.bio.cam.ac.uk
)
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Summary |
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Key words: Asymmetric cell division, Microtubules, Spindle, Par proteins, G-protein signalling, Dynein, Dynactin
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Asymmetry generates diversity |
---|
The direction of division and the ability of a cell to divide symmetrically
or asymmetrically in size is brought about by rearrangement of the
cytoskeleton. We know little about the molecular mechanisms that regulate cell
size asymmetry; however, in the last few years much has been learned about the
targets of these controls. One such substrate is the mitotic spindle and there
is good evidence that its orientation and position in the cell determines the
site of cell cleavage (reviewed by Strome
and Wood, 1983). Asymmetric division can be likened to slicing a
piece of cake (Fig. 1) A
vertical slice divides the cake into two pieces of equal size and content,
both with the same amount of chocolate cake and strawberry icing
(Fig. 1A). However, a
horizontal slice gives two pieces of unequal size and content, a large piece
of chocolate cake and a small piece of cake with all of the icing
(Fig. 1B). If instead of icing
we consider cell fate determinants, it then becomes clear how the orientation
and position of the mitotic spindle and the cleavage furrow direct symmetric
or asymmetric cell division. For example, Drosophila epithelial cells
divide symmetrically along the planar axis of the embryo to produce two
daughters of equal size and mitotic potential. Factors localised at the
basolateral cortex are segregated equally to both daughter cells
(Fig. 1C)
(Matsuzaki et al., 1998
). In
contrast, during neuroblast division localised cell fate determinants such as
Prospero, a homeodomain-containing transcription factor that contributes to
the identity of the GMC, are segregated asymmetrically into the basal GMC
(Fig. 1D) (Doe et al., 1991
;
Matsuzaki et al., 1992
;
Matsuzaki et al., 1998
;
Vaessin et al., 1991
).
Therefore, despite having the same ectodermal origin as epithelial cells,
Drosophila neuroblasts divide asymmetrically and the resulting
daughter cells have distinct cell sizes, mitotic potential and cell fate
(reviewed by Lu et al.,
2000
).
|
Changing from a symmetric to an asymmetric division requires a
reorientation of the division axis. In Drosophila embryonic
neuroblasts, this involves a 90° rotation of the pro/metaphase mitotic
spindle (Kaltschmidt et al.,
2000). In the early C. elegans embryo a 90° rotation
of the centrosome-nucleus complex positions the cleavage plane such that
localised P-granules, which are thought to play a role in germ line
determination in the later embryo, are asymmetrically partitioned to the germ
line precursor daughter (Hyman and White,
1987
; Kemphues and Strome,
1997
; Strome and Wood,
1982
). Additional control of spindle dynamics is necessary when,
as in both Drosophila neuroblasts and the C. elegans zygote,
the generation of daughter cells of distinct cell fates is accompanied by a
difference in cell size. The mitotic spindle plays a key role in setting up
the eccentrically placed cleavage furrow. Until recently the cleavage furrow
in animal cells was thought to form equidistant between the two spindle poles;
however, a growing number of observations show that asymmetry can be achieved
in different ways, both between organisms and within a single organism. Here
we present a short survey of asymmetric cell division, highlighting the recent
findings on the control of spindle positioning and specification of the
cleavage plane in the two-cell nematode C. elegans embryo and
comparing them with results that have been obtained in other systems,
especially the fruit fly, Drosophila melanogaster.
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Cleavage plane induction |
---|
To initiate the cleavage furrow the mitotic spindle must dictate local
changes of the cell surface in the form of either relaxation or contraction of
the cell membrane. Which element of the mitotic spindle, the asters or the
midzone
microtubules¶,
provides that stimulus, remains an important question that has yet to be fully
resolved. Nor is it necessary that all organisms, or even all cells within,
use the same mechanism. Three mechanisms have been proposed by which different
elements of the mitotic spindle could signal to the cell cortex to position
the cleavage furrow (reviewed by Field et
al., 1999; Gatti et al.,
2000
; Oegema and Mitchison,
1997
). According to the astral relaxation model
(White and Borisy, 1983
), the
asters signal to the cell cortex near the poles, inducing it to relax
(Fig. 2A). Alternatively, the
equatorial region of the cell could be induced to contract, either by a signal
from the asters (Fig. 2B)
(Devore et al., 1989
;
Rappaport, 1986
) or from the
overlapping microtubules of the spindle midzone
(Fig. 2C). It is also possible
that both signals act together.
|
Several landmark experiments have addressed whether the spindle asters or
the midzone produce the signal that positions the division plane. Historical
evidence that the spindle asters determine the site of cleavage comes from
micro-manipulation studies on sea urchin eggs
(Rappaport, 1961).
Microsurgical removal of the centre of the egg during the first division
results in a horseshoe-shaped cell with two nuclei. At the next division, the
two spindles produce three cleavage planes: two that bisect each of the
spindles and one extra plane between the two adjacent spindles poles. As a
result, four daughter cells are formed. The outcome of this experiment
suggests that interacting spindle asters control the position of the cleavage
plane, possibly by where they touch the cell cortex. However, this hypothesis
is difficult to verify since there is, as yet, no direct experimental evidence
for such causality. Nevertheless, one possible explanation in support of this
model has been put forward (Foe et al.,
2000
). Foe and co-workers have studied the interactions of spindle
microtubules and the actomyosin cytoskeleton in syncytial Drosophila
blastoderm embryos and find that filamentous actin and cytoplasmic myosin II
are transported towards microtubule plus ends
(Foe et al., 2000
). From these
findings they suggest that cleavage plane induction occurs at sites where
actin filaments attach both to the cortex and to microtubules.
A number of studies in grasshopper neuroblasts
(Kawamura, 1977), newt kidney
epithelial cells and echinoderm eggs
(Rappaport and Rappaport,
1974
) support the model that the midzone microtubules specify the
site of cleavage furrow formation. For example, inserting a small block
between the midzone microtubules and the cell cortex in flattened echinoderm
eggs results in inhibition of cell division
(Rappaport, 1986
;
Rappaport and Rappaport,
1983
). By comparing cleavage activity with the position of midzone
microtubules in cultured epithelial cells
(Cao and Wang, 1996
;
Wheatley and Wang, 1996
), it
was concluded that the signal triggering furrow formation is emitted by the
midzone microtubules. A more exacting experiment would be to eliminate the
astral microtubules specifically and observe whether the midzone on its own is
able to induce a cleavage plane. Bonaccorsi et al. did just this and showed
that spermatocytes and larval neuroblasts from a Drosophila asterless
(asl) mutant could still undergo anaphase and telophase, thus implying
that astral microtubules are not necessary to induce cytokinesis
(Bonaccorsi et al., 2000
;
Bonaccorsi et al., 1998
). It is
difficult in these experiments to be certain that all astral microtubules are
lacking, and it is possible that only a few astral microtubules are sufficient
to induce cytokinesis. Furthermore, it has been shown that cells with
acentrosomal spindles (which resemble anastral spindles in that they also lack
astral microtubules) form bipolar spindles and enter anaphase, but cytokinesis
often fails (Khodjakov and Rieder,
2001
).
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Asymmetric cell division requires an eccentrically placed cleavage plane |
---|
The anterior-posterior polarity of the one-cell C. elegans embryo
is established between the time of fertilisation and the first mitotic
division in response to an external cue provided by the sperm
(Wallenfang and Seydoux,
2000). The next phase in generating polarity is marked by a number
of characteristic changes, which result in the production of two cells
distinct in cell fate and cell size. After the oocyte and sperm pronuclei meet
in the posterior hemisphere, they move to the centre of the embryo
(Albertson, 1984
;
Hyman and White, 1987
).
Following pronuclear migration, the mitotic spindle in the C. elegans
zygote is initially positioned symmetrically along the anterior-posterior
axis. As the spindle grows, one centrosome moves towards the posterior cell
cortex while the other remains relatively stationary, generating a spindle
that is off-centre. Cleavage occurs midway between the two spindle poles
giving rise to a large anterior AB cell and a smaller posterior P1 cell
(Albertson, 1984
).
What are the molecular forces that act on the mitotic spindle to cause this asymmetry? Two types of force that are dependent on microtubules play a role in spindle positioning and spindle pole separation in different model organisms. First a sliding force generated between the overlapping midzone microtubules, possibly mediated by plus-end-directed motor proteins of the kinesin family, could separate spindle poles (Fig. 3A). Second, the astral microtubules on each pole could act, perhaps via the minus-end directed microtubule motor dynein, to drag the spindle poles to opposite sides of the cell (Fig. 3B). In addition, cortical cues could cause microtubules to be selectively destabilised (Fig. 3C) or stabilised (Fig. 3D) in one region of the cell, which would result in an overall imbalance of the microtubule polymerisation forces.
|
A possible mechanism by which such cell polarity cues translate to the
asymmetric spindle positioning in C. elegans has been proposed
(Grill et al., 2001).
Time-lapse analysis of the one-cell C. elegans embryo had previously
shown that the anterior centrosome remains fixed in position, while the
posterior centrosome oscillates and becomes smaller as it moves closer to the
cell cortex (Albertson, 1984
;
Hyman and White, 1987
;
Keating and White, 1998
). The
consequence of such unequal centrosomal movement is an asymmetrically
positioned spindle with the posterior centrosome closer to the cell wall. To
reveal the forces that act on each spindle pole, Grill et al. removed the
central spindle by laser ablation while leaving both spindle poles intact
(Grill et al., 2001
). In
irradiated wild-type embryos, the posterior spindle pole moved faster and
further than the anterior pole. This elegant experiment reveals that pulling
forces act on the spindle poles, and that the posterior shift of the spindle
in wild-type C. elegans zygotes results from a larger pulling force
acting on the posterior pole than on the anterior pole.
The asymmetry of the net forces acting on the two spindle poles is under
control of the par genes (Grill
et al., 2001). In wild-type one-cell C. elegans embryos,
PAR-3 localises to the anterior cortex
(Etemad-Moghadam et al.,
1995
), while PAR-2 localises to the posterior
(Boyd et al., 1996
). The
spindle in both, par-2 and par-3, is centrally positioned
(Kemphues et al., 1988
). After
removal of the central spindle in par-3 mutants, the velocity of both
spindle poles resembles that of the posterior spindle pole in wild-type
zygotes. In contrast, after removal of the central spindle of par-2
mutants both spindle poles move apart with a velocity equal to that of the
anterior spindle pole in wild-type zygotes. This shows that the microtubule
dynamics in the C. elegans zygote are under the control of polarity
factors asymmetrically localised in the cell
(Grill et al., 2001
).
PAR-3 may stabilise or anchor microtubules (reviewed by
Rose and Kemphues, 1998;
Cheng et al., 1995
;
Etemad-Moghadam et al., 1995
)
and there is good reason to think that asymmetrically localised PAR-3 could
act to regulate aster movement by controlling microtubule stability. Only
microtubules on the anterior side of the zygote are stabilised, leaving those
of the posterior aster free to depolymerise. It is intriguing that the
mammalian homologues of the serinethreonine kinase PAR-1, which is localised
to the posterior cortex of the C. elegans zygote, have been shown to
destabilise microtubules (Drewes et al.,
1997
; Ebneth et al.,
1999
). Although no direct effect of PAR-1 on microtubule dynamics
has yet been observed, these findings would support the working model proposed
by Grill et al.: all microtubules of both asters generate equal forces, but
the interactions of the microtubules and the posterior cortex are weaker than
those of the anterior cortex (Grill et
al., 2001
).
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Eccentrically placed cleavage planes |
---|
|
During neurogenesis in Drosophila, neuroblasts delaminate from the
neuroectoderm and undergo asymmetric stem-cell like divisions, generating
another neuroblast and a GMC. In vivo imaging of Drosophila embryos
expressing a GFP (green fluorescent protein) fusion to the microtubule binding
protein tau (Brand, 1995)
reveals that, in embryonic neuroblasts, the mitotic spindle is symmetric and
centrally placed through metaphase. However, at the onset of anaphase, the
microtubules appear to shorten on the basal side of the cell and elongate on
the apical side (Kaltschmidt et al.,
2000
). The overlapping apical and basal astral microtubules, which
are distinctly different in length in Drosopila embryonic
neuroblasts, could specify the eccentric position of the cleavage furrow. The
elongation of the apical astral microtubules towards the emerging GMC occurs
before the cell membrane starts to pucker, and membrane invagination occurs
before the midbody moves towards the cleavage furrow
(Kaltschmidt et al., 2000
).
The eccentric placement of the cleavage plane in Drosophila embryonic
neuroblasts might, therefore, support the postulated role of astral
microtubules in specifying the site of the cleavage furrow as described above
(reviewed by Oegema and Mitchison,
1997
). In contrast, in Drosophila asl and centrosomin
(cnn) mutants, larval neuroblast divisions are still asymmetric, in spite
of partially defective mitotic centrosomes and the absence of detectable
astral microtubules (Bonaccorsi et al.,
2000
; Megraw et al.,
2001
; Megraw et al.,
1999
; Vaizel-Ohayon and
Schejter, 1999
). Giansanti et al. postulate that the eccentric
position of the cleavage plane in Drosophila neuroblasts is defined
by signals originating from the midbody, and it is the asymmetric position of
the midbody that leads to the overall spindle asymmetry
(Giansanti et al., 2001
). It
is interesting to note that these two types of asymmetric division, an
asymmetric division reminiscent of that seen in the C. elegans zygote
and an asymmetric spindle similar to that described for Drosophila
neuroblasts, can exist within the same lineage, such as that of the
Drosophila sensory organ precursor (SOP) cells
(Roegiers et al., 2001
).
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Possible controls of cleavage plane positioning |
---|
Giansanti et al. suggest that in Drosophila neuroblasts the shift
of the midbody towards the GMC occurs via a mechanical link between the
cortex, nucleus and midbody (Giansanti et
al., 2001). Alternatively, one could imagine a mechanism whereby
astral microtubules on the basal spindle pole of Drosophila
neuroblasts are induced to depolymerise while those of the apical aster are
stabilised, resulting in a larger apical and smaller basal aster that together
constitute an asymmetric spindle. This model agrees with a role of astral
microtubules in the placement of the cleavage plane as previously suggested
(Rappaport, 1961
). Certainly,
both this model and that of mechanical linkage predict a specialised site on
the GMC cortex to facilitate local interaction between the spindle
microtubules and the cell cortex. If such an interaction actively destabilises
microtubules locally, then polymerisation forces would become unbalanced,
resulting in either asymmetrically positioned asters and/or differently sized
asters.
Bearing in mind the requirement for asymmetrically stabilised spindle poles
during asymmetric cell division, it is intriguing that all the above mentioned
examples of eccentrically placed spindles share an asymmetry in the morphology
of their centrosomes and the microtubules they produce. For example, the
anterior aster of the asymmetrically-positioned spindle of the C.
elegans zygote is large and has many microtubules, while the posterior
aster appears flattened and smaller and has fewer astral microtubules
(Keating and White, 1998). A
difference in aster size and morphology has also been described for the
divisions of the four-cell sea urchin embryo. The micromere centrosomes
contain less centrosomal material than the macromere poles
(Holy and Schatten, 1991
) and
the macromere aster is spherical, whereas the micromere aster undergoes
elongation during late anaphase and telophase and is flattened perpendicular
to the spindle axis (Holy and Schatten,
1991
). Note, however, that it is possible that micromere
centrosomes contain the same material but are merely more condensed than the
macromere centrosomes. The unique morphology of the micromere aster in sea
urchin embryos has been suggested to be due to proximity to the plasma
membrane (Dan and Nakajima,
1956
). As the two centrosomes have already begun to become
distinct in metaphase (Holy and Schatten,
1991
), this must also reflect an intrinsic difference between the
two microtubule organising centres. In Drosophila embryonic
neuroblasts, as the astral microtubules become longer and more abundant at the
beginning of anaphase, the apical aster enlarges. The basal aster is
concomitantly reduced in size and the basal centrosome has reduced levels of
the centrosomal proteins
-tubulin, CP60 and CP190
(Kaltschmidt et al., 2000
).
This was found also to be the case for larval Drosophila neuroblasts
(Bonaccorsi et al., 2000
;
Ceron et al., 2001
).
Microfilaments may be part of the spindle-positioning machinery in several
organisms. First, actin has been reported to localise temporarily to the
anterior region of the C. elegans zygote
(Hill and Strome, 1988;
Strome, 1986
) and asymmetric
positioning of the mitotic spindle is inhibited by disrupting microfilaments
with cytochalasin D during a narrow time interval in the first cell cycle
(Strome and Wood, 1983
).
Second, an enrichment of actin has also been postulated to play a role in
establishing cortical polarity in the mouse egg
(Longo and Chen, 1985
). In
immature mouse oocytes actin is cortical, while in mature eggs it is
asymmetrically localised. When induced to undergo maturation, the meiotic
spindle forms in the centre of the oocyte and then moves towards the
actin-rich periphery, where it becomes anchored to the plasma membrane
(Chambers, 1917
;
Conklin, 1917
;
Longo and Chen, 1984
).
Disruption of microfilaments with cytochalasin B inhibits this movement.
Third, actin has also been shown to localise asymmetrically in
Drosophila larval neuroblasts
(McCartney et al., 1999
) and
it is possible that localised actin functions (possibly only briefly) to set
up or respond to the spatial cues that are needed to establish the asymmetry
in the spindle of Drosophila larval neuroblasts.
What are the factors known to be necessary for induction of spindle
asymmetry in embryonic Drosophila neuroblasts, and how are they
regulated during the embryonic neuroblast cell cycle? First, Inscuteable [a
protein of 859 amino acids encoding a putative SH3 target site, ankyrin
repeats and a PDZ-binding domain (Kraut
and Campos-Ortega, 1996)] localises as an apical crescent in
neuroblasts from late interphase until anaphase
(Kraut et al., 1996
) and is
both necessary and sufficient to direct apical-basal cell division in
neuroblasts (Knoblich et al.,
1999
; Kraut et al.,
1996
; Tio et al.,
1999
). In inscuteableP72 null embryos, the
mitotic spindle fails to rotate and the direction of neuroblast division is no
longer strictly apical-basal (Kaltschmidt
et al., 2000
; Kraut et al.,
1996
). Several proteins are required to localise Inscuteable. Pins
(Partner of Inscuteable), a tetratrico-peptide (TPR) repeat protein, binds to
Inscuteable and shows an almost identical subcellular localisation
(Parmentier et al., 2000
;
Schaefer et al., 2000
;
Yu et al., 2000
). Inscuteable
localisation is established but not maintained in pins mutants and as
a consequence the mitotic spindle in embryonic neuroblasts is misoriented.
Pins encodes three `GoLoco' motifs, which are present in proteins that bind
the subunits of heterotrimeric G-proteins, G
0 and
G
i (Schaefer et al.,
2000
). G
0/G
i, together with
Gß
, comprise the G-protein complex and are involved in the
organisation of the actin cytoskeleton and asymmetric localisation of cortical
proteins in several different organisms (reviewed by
Chant, 1999
;
Jin et al., 2000
). Schaefer et
al. have recently shown that, in Drosophila embryonic neuroblasts,
Inscuteable functions via Pins as an apical adaptor for G
i,
which in turn sets up a polarity cue at the apical neuroblast cortex
(Schaefer et al., 2001
). In
addition, overexpression of G
i in neuroblasts produces two
equal-sized daughter cells (Schaefer et
al., 2001
). The heterotrimeric G-protein cascade, which is
confined to the apical cell cortex, thereby mediates asymmetric neuroblast
division, possibly via reorganisation of the actin cytoskeleton (reviewed by
Schweisguth, 2000
). G
is also required for correct positioning and morphology of the mitotic spindle
in the C. elegans zygote (reviewed by
Gotta and Ahringer, 2001a
;
Gotta and Ahringer, 2001b
).
Thus, G-protein signalling during spindle orientation may be a process
conserved between Drosophila and C. elegans.
Gotta and Ahringer suggest that G-protein signalling may function to
connect spindle position and polarity in C. elegans
(Gotta and Ahringer, 2001a).
The mammalian homologue of Pins, Ags-3, functions as a receptor-independent
activator of G-protein signalling
(Takesono et al., 1999
). In
C. elegans simulatenous inhibition of two genes with weak homology to
Pins (ags-3.2 and ags-3.3) recapitulates the phenotype of
embryos lacking G
activity: asymmetric spindle positioning is affected
as is the generation of different-sized daughter cells [M. Gotta and J.
Ahringer, personal communication; S. Grill, P. Gonczy and A. Hyman, personal
communication (Gotta and Ahringer,
2001a
)]. In Drosophila pins mutants a large number of
larval neuroblasts divide symmetrically
(Parmentier et al., 2000
),
although this has not been observed in embryonic neuroblasts
(Schaefer et al., 2000
;
Yu et al., 2000
), possibly due
to maternal Pins protein being present and sufficient for embryonic
divisions.
Lu et al. have shown that adherens junctions are responsible for the
default, planar orientation of the mitotic spindle in epithelial cell
(Lu et al., 2001). RNAi
against the epithelial-cell-enriched (E)-adenomatous polyposis coli (APC)
tumor suppressor protein and microtubule-associated protein EB1 (both of which
are adherens-junction-associated proteins), causes epithelial cells to switch
from a symmetric to an asymmetric division pattern
(Lu et al., 2001
). This
implies a possible function of adherens junctions in preventing asymmetric
cell division. It is noteworthy, however, that cells in the procephalic
neurogenic region (PNR) have adherens junctions but nonetheless divide
asymmetrically.
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A role for the dynein-dynactin complex in generating asymmetry? |
---|
In the C. elegans zygote, cytoplasmic dynein and dynactin are
required during pronuclear migration, centrosome positioning and pronuclear
rotation (Gönczy et al.,
1999; Skop and White,
1998
). Cytoplasmic dynein is further involved in maintaining the
tight association between the centrosomes and the male pronucleus. Gönczy
et al. suggest a mechanism by which cytoplasmic dynein, anchored to the
pronucleus, drives centrosome separation. This model predicts that the pulling
forces required during centrosome separation are provided by interactions
between cytoplasmic dynein anchored on the nuclear membrane and astral
microtubules (Gönczy et al.,
1999
).
The dynein-dynactin complex has also been implicated in the rotation of the
centrosome-nucleus-complex in the C. elegans P1 cell
(Skop and White, 1998;
Waddle et al., 1994
). The
original model suggested a cortical capture mechanism
(Hyman and White, 1987
). Laser
microsurgery experiments identified a cortical site rich in actin,
actin-capping proteins and dynactin
(Hyman, 1989
;
Waddle et al., 1994
). Reducing
the levels of two orthologues of the C. elegans dynactin complex
results in misalignment of the spindle in the P1 cell
(Skop and White, 1998
). By
localising to the cell cortex, dynactin may both tether microtubule ends and
bind to the minus-end directed, microtubule-associated dynein, thereby
activating its motor activity. While tethered to the cell cortex, dynein could
reel in one aster by moving along astral microtubules, depolymerising and
shortening them (Skop and White,
1998
; Waddle et al.,
1994
). An alternative interpretation of P1 spindle misalignment is
that the spindle is displaced to an eccentrically localised cortical site as a
result of asynchronous ingression of the first cleavage furrow
(Gönczy et al., 1999
).
This would imply that the dynein-dynactin complex controls the position of
spindle attachment.
In Drosophila embryonic neuroblasts, a subunit of dynactin, p150Glued, is localised in a basal cortical crescent before it is asymmetrically segregated to the GMC cortex (J.A.K. and A.H.B., unpublished). It is possible that, by binding to dynactin at the GMC cortex, dynein mediates both the rotation of the pro/metaphase spindle and the difference in length of astral microtubules in the neuroblast.
![]() |
Common themes in generating cell diversity |
---|
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Acknowledgments |
---|
![]() |
Footnotes |
---|
Cell fate determination demands a stable change in the interior of the
cell. A cell is characterised by fate determining factors (also called `cell
fate determinants'), such as proteins and mRNAs. Presence and absence in the
cell can result in daughter cells having properties different from each other.
For example, the presence or absence of transcription factors can result in
gene expression being turned on or off. In yeast, the ability to switch mating
type is determined by HO endonuclease, whose transcription is repressed by
Ash1p (asymmetric synthesis of HO endonuclease)
(Bobola et al., 1996
;
Sil and Herskowitz, 1996
).
Ash1p is present in the daughter but not in the mother, resulting in HO
endonuclease expression and mating type switching in the mother, but not in
the daughter (Nasmyth et al.,
1987
).
¶ Anaphase is characterised by a shortening of the kinetotchore microtubules
resulting in the poleward movement of sister chromatids (anaphase A) followed
by the elongation of polar microtubules (anaphase B) leading to separation of
the two spindle poles (see
also||).
|| Microtubules are the primary structural component of the mitotic spindle.
The polarity of the spindle microtubules is such that the minus ends are at
the centrosomes and the plus ends directed towards the cell cortex (or
chromosomes). There are three different kinds of spindle microtubule, each
named after the position of the plus end. The first class, kinetochore
microtubules, extend from the centrosome to the kinetochores and are important
for the segregation of the chromosomes to the spindle poles during anaphase.
The second class, astral microtubules, stretch from the centrosome towards the
periphery, with their plus ends contacting the cell cortex. This interaction
is important for spindle positioning and cleavage plane localisation during
cytokinesis. The third kind are midzone microtubules, which reach from one
centrosome into the spindle midzone towards the other centrosome. While
midzone microtubules from opposite centrosomes interact, they generate an
outward force through antiparallel sliding, which counteracts the inward
forces generated by the kinetochores.
![]() |
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