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Martha C. Soto
Assistant Professor
UMDNJ-RWJMS
Department of Pathology
Room 231
Piscataway. NJ 08854
(732) 235-4424
FAX - 4825
sotomc@umdnj.edu
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Using C. elegans embryos to
investigate polarized cell divisions and polarized cell migrations
during development
Proper control of cell polarity is
essential for all cells. Healthy mammalian epithelial cells maintain apical
basal polarity. while cancerous epithelial cells exhibit defects in the
orientation of their division axis. Our studies using the nematode C. elegans
combine genetic. molecular and biochemical approaches to investigate how
specific proteins are used to regulate cell divisions and cell migrations at key
points in development. Our lab focuses on two aspects of cell polarity:
We have uncovered a role for the major
embryonic cyclin dependent kinase. CDK-1. in controlling the polarity of the
EMS division. We found a CDK-1 mutation that affects cell polarity but does not
interfere with the cell cycle. CDK-1 therefore has a role in EMS spindle
rotation and cell fate. This suggests that cell cycle regulators like CDK-1 are
also regulators of polarized cell divisions. perhaps because the decision for
how to set up the division axis is best coupled to a specific time in the cell
cycle. Genetic experiments have suggested possible targets for CDK-1 in this
polarity function. One exciting avenue for research will be to identify the
CDK-1 targets that carry out its polarity function. perhaps by regulating
cytoskeletal proteins.
| (1) How do
cell cycle proteins contribute to polarized cell divisions?
In C. elegans embryos signaling
between cells begins at the four-cell stage. The P2 cell must be in contact
with the EMS cell in order for P2 to send a signal to EMS which induces it
to undergo a spindle reorientation and to create two daughters of distinct
cells fates. Screens for mutations affecting the fate of EMS have revealed
that the polarizing signal from P2 to EMS involves two partially redundant
pathways. a wingless(WG/WNT) pathway and another pathway involving the
tyrosine kinase SRC-1. One project in the lab focuses on how cell cycle
components contribute to the P2 to EMS signal. |
Figure 1: Four cell embryo and the EMS lineage.
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| Figure 2. Epidermal movements.
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GEX proteins
and the control of epidermal morphogenesis.
Once cells acquire a
specific fate. they must undergo cell shape changes and movements to form
tissues and organs. The C. elegans epidermis. often referred to as
the hypodermis. first forms as a cap of cells on the dorsal side of the
embryo (Figure 2.) As soon as the epidermal cells differentiate. they
initiate cell shape changes and organize into rows of cells. The cells then
migrate to eventually enclose the embryo. The underlying mechanisms that
control these events are largely not understood. GEX-2 and GEX-3 are two
novel proteins. conserved from worms to humans. which are essential for the
earliest movements of the epidermal cells. gex stands for gut
on the exterior. the terminal phenotype of mutant embryos. gex genes genetically interact with mutations in the C. elegans homologs of Rac GTPases. Since Rac GTPases are known to regulate actin
polymerization. our working hypothesis is that GEX-2 and GEX -3 are
regulators of the actin cytoskeleton. In support of this. a third gex gene we cloned. GEX-1. is a homolog of human WAVE1. an activator of the
Arp2/3 complex. a 7-protein complex that directly binds actin to promote its
polymerization. We are pursuing experiments to test the model that GEX1. GEX-2 and GEX-3 are directly regulating the Arp2/3 complex in order to get
cells to change their shape and initiate cell migrations. Further genetic
screens will allow us to search for the upstream signals that initiate the
cell migrations by regulating GEX-1. GEX-2 and GEX-3. |
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