Basic HTML Version
Poster Full Abstracts - Cell Death
Poster board number is above title. The first author is the presenter
222
substrates by binding to Ago and inhibiting its Ub ligase activity.
335B
Non-Cell Autonomous Regulation of Hippo signaling in Drosophila by the Hedgehog receptor Patched.
Jacob Daniel Kagey
1,2
, Jordan Brown
2
,
Kenneth Moberg
2
. 1) Biology, University of Detroit Mercy, Detroit, MI; 2) Cell Biology, Emory University School of Medicine, Atlanta, Ga.
We conducted a Flp/FRT based EMS screens for mutations on chromosome 2R that confer a growth advantage conditional upon a block in cell death.
From this screen, we identified an allele of patched,
ptc
B.2.13
. Immortalized
ptc
B.2.13
mutant clones lead to dramatic increases in eye and wing size, mainly by
expanding wild type tissue, suggesting Ptc normally functions as a non-autonomous growth suppressor. At the molecular level, the
ptc
B.2.13
mutation results
in the autonomous increase of the Hedgehog pathway, including the activation of the downstream transcriptional factor, Cubitus Interuptus (Ci).
Additionally, we observe an increase of several known Ci transcriptional targets, including Decapentaplegic (Dpp). This aberrant production of Dpp in
ptc
B.2.13
cells creates ectopic gradients of Dpp signaling radiating from mutant clones into surrounding wild type tissue. These gradients of Dpp activate
Mothers Against Decapentaplegic (pMad), with the most robust activation observed in wild type cells immediately adjacent to mutant clones. This activation
spatially correlated with the increase of several targets of the potent pro-growth transcription factor Yorkie (Yki). Yki can function as a co-activator with
pMad, specifically in the transcriptional activation of the pro-growth miRNA,
Bantam
. Domains of pMad activation surrounding
ptc
B.2.13
clones also
correspond to regions of increased cellular proliferation, suggesting the ectopic activation of pMad may be driving the overgrowth phenotype. In testing this
hypothesis, we find that a single loss of function
Bantam
allele is capable of dominantly suppressing the overgrowth phenotype, suggesting a model where
the clonal loss of Ptc leads to a Dpp/Yki dependent non-autonomous increase in proliferation. Given the frequent loss of the human Ptc1 gene in basal cell
carcinomas and medulloblastomas, this model could have implications for the pathogenesis of a subset of human cancers.
336C
Identifying novel components of the Fat cadherin pathway.
Srdjana Ratkovic, Helen McNeill. Samuel Lunenfeld Research Institute, Mt. Sinai Hospital,
Toronto, Ontario.
fat
is a
Drosophila
tumor suppressor gene that encodes a large cadherin involved in regulation of growth and a form of tissue organization called planar
cell polarity (PCP). Fat regulates growth through its actions upstream of the Hippo kinase pathway, however the precise mechanism of its action is still
unknown and very few proteins that biochemically associate with Fat have been identified. To better understand the biology of Fat signaling, I am using a
proteomic screening approach to identify novel Fat interactors using affinity purification coupled with mass spectrometry. I generated flies and KC167 cells
that overexpress truncated versions of tagged Fat protein, which are used as bait in these studies. Potential Fat interactors will further be evaluated for effects
on growth, and how they genetically and biochemically interact with Fat.