Dan
Marston
Postdoc
Using C. elegans
to
understand the molecular mechanisms of cell
positioning during development
 In the C. elegans
embryo, gastrulation begins at
the
26-cell stage with the migration of the two endoderm precursor cells,
Ea and Ep, from the surface of the embryo to the embryonic interior.
The cellular process driving this ingression of the Ea and Ep cells is
an actin-myosin dependent constriction of the apical surface of these
cells. Comparison with other systems would suggest that in order for
this apical constriction to lead to ingression it is essential that
cell-cell adhesion be maintained between the Ea and Ep cells, and/or
the surrounding cells during the constriction. Supporting this is the
observation that the surrounding cells are in close contact with the
ingressing cells and they move round to cover the Ea and Ep cells as
those cells move in to the embryo.
 There are more than 35 genes in the C.
elegans
genome thought to encode adhesion proteins comprising several
different classes, including cadherin proteins and IgCAMs. Currently
there are no reported defects in gastrulation in strains carrying
mutations in these genes. Furthermore when we used feeding RNAi to
disrupt the function of those genes for which there is no mutant we
detected no defects in gastrulation. One hypothesis is that there may
be redundancy between multiple adhesion proteins.
One way to
overcome the challenge presented by redundancy is to inhibit the
function of multiple adhesion proteins simultaneously. It is possible
do this by microinjecting adult hermaphrodites with small pools of
dsRNAs that code for different proteins. The adults then lay embryos
with reduced expression of the proteins coded for by the pooled dsRNAs.
Using this technique we have attempted to disrupt the function of
multiple proteins that contain cadherin domains. We have identified a
group of these proteins that are required for normal embryonic
development. Furthermore we have been able to use 4D microscopy to
follow cell migrations in embryos dissected out of the dsRNA treated
adults to investigate the effects of reducing the function of these
cadherin-domain containing proteins on cell movements during
gastrulation.
Publications as a postdoc:
Marston, D.J., M. Roh, A. Mikels, R. Nusse,
and B. Goldstein. Wnt
signaling during C. elegans embryonic development. Methods in
Molecular Biology (in press).
Lee,
J-Y*, DJ Marston*, T Walston,
J Hardin,
A
Halberstadt and
B Goldstein (2006)
Wnt/Frizzled Signaling Controls C. elegans Gastrulation by Activating
Actomyosin Contractility
Current Biology 16:1986-1997.
* contributed equally
Marston, D.J.
and B. Goldstein (2006)
Symmetry Breaking in
C. elegans: Another Gift from the Sperm.
Developmental Cell 11:273-274.
Marston,
D.J. and B. Goldstein (2006)
Actin-based forces
driving embryonic
morphogenesis in C. elegans
Current Opinion in Genetics and
Development 16: 392-398.
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Talks
at National Meetings:
2008
C. elegans Development Meeting, Madison, WI
MRCK
Drives Apical Constriction in C. elegans Gastrulation by Activating
Myosin
2007
ASCB Meeting
Atypical
Cadherins Are Required for Cell Movements during C. elegans Gastrulation
2007
International C. elegans Meeting, Los Angeles, CA
Polarised
cell movements during gastrulation require PAR-1 and atypical cadherin
adhesion proteins.
2006
C. elegans Development Meeting, Madison, WI
Wnt/Frizzled
Signaling Controls C. elegans Gastrulation by Activating Actomyosin
Contractility
2005
International C. elegans meeting, Los Angeles, CA, Cell Biology,
Adhesion and Migration Session
Investigation
of a role for cadherin-domain containing proteins in C.
elegans gastrulation
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Honors and Awards:
Selected to give a talk at the 2008 C. elegans Development Meeting!
Dan was awarded a 2007-2008 UNC Postdoctoral Award for Research
Excellence!
Awarded the prize for best poster by a postdoc, 2007 Southeast Regional
Developmental Biology Meeting!
Selected to give one of the New & Notable Plenary Talks at the 2006
C. elegans Development Meeting!
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