Biomedical Engineering Reference
In-Depth Information
4. SPINDLE ORIENTATION AND MTOC POSITIONING
In other organisms, the PCP pathway controls spindle orientation. In
C. elegans
, some components of the Wnt/
b
-catenin asymmetry pathway reg-
ulate spindle orientation in at least some of the asymmetrically dividing cells. In
the normal EMS cell, spindle is initially aligned along the left-right axis and
rotates to adopt the anterior-posterior orientation until anaphase. In mutants
of
mom-2
/Wnt and
mom-5
/Fzd, spindle fails to rotate (
Schlesinger, Shelton,
Maloof, Meneghini, & Bowerman, 1999
). In addition, two of the three Di-
shevelled homologues (DSH-2 and MIG-5) redundantly control spindle ori-
entation in the EMS cell (
Walston et al., 2006
). In contrast, spindle is normal in
wrm-1
/
b
-catenin and
apr-1
/APC mutants. Therefore, the pathway appears to
be split into three at the DSH proteins: regulation of spindle orientation,
WRM-1 localization, and SYS-1 localization. Although
gsk-3
/GSK3
b
was
previously reported to be required for EMS spindle orientation (
Schlesinger
et al., 1999
),
gsk-3
(
RNAi
) embryos have earlier defects in the transition from
meiosis tomitosis in fertilized eggs (
Nishi & Lin, 2005; Shirayama et al., 2006
).
Therefore, its function in the EMS division needs to be reexamined.
The EMS spindle orientation is also controlled by another cell-cell inter-
action between the EMS and P2 blastomeres that involves a transmembrane
protein MES-1 and SRC family tyrosine kinase SRC-1 (
Bei et al., 2002
).
MES-1 is required in both EMS and P2, while SRC-1 is required in
EMS. Interestingly, bothMES-1 and SRC-1 regulate polarity and spindle ori-
entation in P2 in response to MES-1 itself in EMS (
Arata, Lee, Goldstein, &
Sawa, 2010; Berkowitz & Strome, 2000
). It has been proposed that a
homophilic interaction between MES-1 at the boundary of EMS and P2
aligns spindle of EMS and P2 in the same orientation, which resembles the
PCP regulation (
Arata et al., 2010
). However, the mechanism of spindle
regulation appears to be distinct between these cells. It has been recently
reported that GPR (G protein regulator; homologues of Pins in
Drosophila
)
proteins that control spindle pulling forces preferentially localize to the
EMS-P2 boundary in P2 but not in EMS (
Werts, Roh-Johnson, &
Goldstein, 2011
). Therefore, in P2, spindle alignment is likely to be
regulated by cortical pulling forces produced by GPR proteins on the
P2-EMS boundary. However, the mechanism in EMS is still obscure.
During telophase of the EMS division, the posterior but not the anterior
centrosome-nuclear complex moves toward the posterior cell cortex to
