Contractile Proteins and the Cytoskeleton in Morphogenesis
and Wound Healing
Our intellectual focus is on identifying determinants
of cell shape that function during development. Utilizing
molecular genetic and reverse genetic approaches in
Drosophila, we have shown that conventional nonmuscle
myosin is necessary for driving both cell division
and post-mitotic cell shape changes for morphogenesis,
and cellular locomotions. Currently, we are investigating
how myosin elicits cell shape change and how its function
is regulated through filament formation, phosphorylation,
sub-cellular targeting and small GTP-binding protein
function.
We are characterizing myosin light chain kinase;
a novel myosin VII heavy chain; and additional elements
that participate in localizing myosin and transmitting
the forces that it produces. We used screens for aberrant
cell shape induced in the yeast S. pombe by expression
of transfected Drosophila cDNAs. These experiments
show that elements that define cell shape are conserved
throughout phylogeny and that a screen in yeast is
a valuable tool for recovering heterologous cDNAs
that encode cytoskeletal elements and the proteins
that regulate them. In the fly, we are identifying
gene products that are necessary for myosin function
by genetically recovering second site non-complementing
loci and biochemically recovering proteins that bind
to myosin. To date, our experiments identify ~30 loci
that genetically interact with myosin and a kinase
activity that phosphorylates myosin heavy chain and
establish genetically that the Rho signalling pathway
is required in concert with nonmuscle myosin II for
morphogenesis.
We are also using manipulation studies to understand
the forces that drive cellularization and morphogenesis.
We show that both the amnioserosa and the leading
edge of the lateral epidermis contribute to the movements
of dorsal closure.
Finally, we are examining the role these proteins
play in movements that occur during wound healing.
Together, our experiments promise to reveal the nature
of cytoskeletal function in cell shape determination
for cell division and morphogenesis throughout development.
Rotation students and students who formally accept
the lab for their Ph.D. work are treated like much
like colleagues that are intellectually responsible
for driving a project related to the PI's overall
interests. Technical and intellectual training is
provided by the PI and other lab members. Students
are required to participate in and present at lab
meetings and national scientific meetings. Regular
meetings between the PI and the students are planned
for every 2-3 weeks.
