Orienting the Mitotic Spindle: An optogenetic approach Oriented cell divisions (OCDs) are essential to control tissue development and homeostasis. They participate to fate determination of daughter cells, stem cell proliferation and tissue growth. Defects of OCD are thus involved in tumour progression and developmental diseases. Although the core mechanisms orienting the mitotic spindle downstream polarity cues are partly understood, little is known about the fine spatiotemporal orchestration of this process. How are conflicting polarity signals

spiritualblurtedAI and Robotics

Nov 24, 2013 (3 years and 6 months ago)

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Orienting the Mitotic Spindle: An optogenetic approach


Oriented cell divisions (OCDs) are essential to control tissue development and
homeostasis. They participate to fate determination of daughter cells, stem cell
proliferation and tissue growth. Defects of OCD are thus involved in
tumo
u
r

progression
and deve
lopmental diseases. Although the core mechanisms orienting the mitotic
spindle downstream polarity cues are partly understood, little is known about the fine
spatiotemporal orchestration of this process. How are conflicting polarity signals
balanced?
How d
oes the timing of these signals determine their integration?
What are
the modulators involved?
In this
work
we raise the question of the signal processing
from cortical polarity cues down to the force generation and orientation of the mitotic
spind
le.
Using a novel approach combining micro
-
patterning and optogenetics, I
am
study
ing

the sensitivity of OCD to polarity cues (components of the Par and LGN
complexes) and its robustness to conflicting signals (interfering gradients, polarity vs
geometry).

What is the minimum level of polarity signal required to precisely orient cell
division? What signal is amplified or filtered to obtain a sensitive but robust output?

To
a
nswer these questions, I
use
a state
-
of
-
the
-
art
light
-
controlled method to recruit
p
olarity cues at the cell cortex of dividing cells
, and measure the sensitivity
and
robustness
of mitotic spindle orientation to varying amounts of
precision in the polarity
information.
I will infer from these results how the signal is processed from polar
ity
cues to spindle orientation.

Here I present the tools
and methods
that I have developed
in order to study oriented cell division at the systems level.