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Poster Full Abstracts - Cell Biology and Signal Transduction
Poster board number is above title. The first author is the presenter
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border cell migration. We identified additional novel genes that likely function in diverse cellular pathways, many of which have not yet been studied in the
context of cell migration in any organism. Furthermore, we demonstrated that a targeted, well-designed screen is sufficient to discover new candidate
regulators of collective border cell migration with minimal time and effort.
225C
TGF-β/Activin signaling mediates border cell migration during Drosophila oogenesis.
Sameen Babur, Maryanna Aldrich, Takuya Akiyama, Kristi
Wharton. Department of Molecular Biology, Cell Biology, & Biochemistry , Brown University, Providence, RI.
The development of vastly diverse organisms requires the properly timed migration of both single cells and cohesive clusters of cells. These cells gain
invasive properties and are directed to their destinations through various guidance factors and cues. Elucidating this highly complex cellular behavior in the
context of both normal development and the misregulated occurrence of cancer metastasis requires understanding the intricate molecular mechanisms
controlling cell migration. Border cell migration during Drosophila oogenesis provides an excellent in vivo system to visualize and identify the many
interacting factors involved in the phenomenon of collective cell migration. In this process, nonmigratory polar cells that lie at the anterior end of each
Drosophila egg chamber induce the surrounding follicle cells to become invasive, migratory border cells through the action of JAK-STAT signaling. A
cluster of two polar cells and four to eight border cells subsequently delaminates from the anterior end of the egg chamber and collectively migrates
posteriorly to the oocyte. We have identified an important role for TGF-β/Activin signaling in this process, as disruption of this signaling pathway via RNAi
in either the border cells or the polar cells leads to a significant migration delay. This effect is specific to the migratory behavior of these clusters, as
reduction of TGF-β/Activin signaling does not affect border cell specification, cluster delamination, or cluster cohesiveness. As seen in other cases of
delayed cluster migration, we observe a mislocalization of E-cadherin when TGF-b/Activin signaling is reduced. Finally, we find that the effect of TGF-
β/Activin signaling on border cell migration appears to be independent of a role for the related BMP signaling pathway.
226A
Genetic screening to identify enzymes affecting the spread of ovarian cancer.
Neville Cobbe, Sarah Forrester, Jenny Horend, Hussain Jaffery, Sally
Quine, Amy Rothwell, Shaun Speldewinde, Sarah Taylor, Adriana Guillermo Wiesinger, Helen Young, Daimark Bennett. School of Biological Sciences,
University of Liverpool, Liverpool.
Ovarian cancer is an aggressive form of carcinoma that is regrettably difficult to detect before metastasis, rendering treatment very difficult. Our goal is to
understand the cause and mechanisms of this invasive cell migration by using the fruit fly,
Drosophila melanogaster
. During normal development of the
Drosophila
ovary, a specialized group of epithelial cells (known as the border cell-cluster) migrates through the egg chamber in a manner akin to the
invasive migration of ovarian cancer cells. As border cell migration can be readily visualized microscopically, this provides a powerful model system to
study the mechanics of ovarian cancer metastasis
in vivo
, with conserved genes previously implicated in both processes alike. Our major focus is on the way
cancers are controlled by reversible phosphorylation, by identifying kinases and phosphatases affecting border cell migration. We have compiled an
extensive database of conserved
Drosophila
kinases and phosphatases, using this to design genetic crosses in which a short hairpin RNA (shRNA) could be
specifically produced under the control of the GAL4 transcription factor expressed ectopically within border cells, ideally leading to depletion of a particular
enzyme within the border cells by means of RNA interference (RNAi). Here we will present and discuss the results of two successive genetic screens
performed blindly with UAS-shRNA lines from different sources, which have been retrospectively validated by identification of enzymes independently
characterized as important for border cell migration.
227B
The role of fd64a in salivary gland migration.
Caitlin D. Hanlon, Deborah J. Andrew. Cell Biol, Johns Hopkins Med Inst, Baltimore, MD.
Drosophila fd64a encodes a member of the fork head box family of transcription factors. Most closely related to mammalian FoxL, fd64A is dynamically
expressed in embryos in several tissues, including the somatic muscles, the caudal visceral mesoderm, the ventral longitudinal muscles, and the hindgut.
fd64A expression in a subset of somatic body wall muscles in thoracic segments T2 and T3 is especially intriguing due to the intimate association of these
muscles with the migrating embryonic salivary gland. The goal of this project is to determine if and how fd64a affects salivary gland migration, and to
identify and characterize the relevant Fd64a targets. To investigate the role of fd64a in salivary gland migration, two overlapping deficiencies removing the
fd64a gene were assayed for defects in salivary gland morphology and placement. Staining with apical membrane and nuclear markers show a range of
salivary gland defects in embryos homozygous for each deficiency and in embryos carrying the two deficiencies in trans, including rough, stunted, and mis-
positioned glands. We have also created UAS-fd64A transgenic fly lines that allow for expression of the gene in new places. Ectopic expression of fd64a
using twist-Gal4, which drives expression in all mesoderm, causes the salivary gland to curl and bend. These data support a role for fd64a in directing
salivary gland migration. Based on these promising preliminary findings, we are now creating a null allele of fd64a to fully characterize its role in salivary
gland migration and to use as a tool to find the relevant downstream effectors.
228C
Par-1 Controls Non-Muscle Myosin II Activity Through Myosin Phosphatase to Regulate Collective Border Cell Migration.
Pralay Majumder
1
,
Aranjuez George
1,2
, McDonald Jocelyn
1,2
. 1) Molecular Genetics, Lerner Research Institute, Cleveland Clinic, Cleveland, OH; 2) Genetics, Case Western
Reserve University School of Medicine, Cleveland, OH.
Many cells migrate in collective groups during tissue morphogenesis, wound healing, tumor invasion and metastasis. In single migrating cells, localized
actomyosin contraction couples with actin polymerization and cell-matrix adhesion to regulate cell protrusions and retract trailing cell edges. In contrast, we
have only a limited understanding of mechanisms that coordinate actomyosin dynamics in collective cell migration. We study the migration of Drosophila
border cells (BCs), which move as a cohesive group of 6-10 epithelial-derived cells during late oogenesis. We previously observed that mutants of the cell
polarity protein Par-1, a serine-threonine kinase, result in defective border cell epithelial detachment and migration. We now show that these defects are
caused by perturbations in cytoskeletal dynamics due to disruption of a previously unknown signaling pathway between Par-1 and non-muscle myosin-II
(Myo-II). Using live imaging, we show that Myo-II is required for two critical features of BC migration: detachment of BCs from the surrounding
epithelium, and extension of cell protrusions of normal length and lifetime. We identified a robust genetic interaction between the myosin regulatory light