organisation - the Instituto Gulbenkian de Ciência

THE HIPPO TUMOR SUPPRESSOR PATHWAY AND THE SRC PROTO-ONCOGENE
REGULATE DISTINCT F-ACTIN NETWORKS.
Eukaryotic cells generate a diversity of F-actin networks. We observed that
Hippo and Src signaling activities control distinct F-actin webs at specific subcellular
locations. Moreover, we identified ABPs specifically involved in mediating
Hpo or Src signaling activities. This argues that the geometrical, mechanical
and dynamic properties of each F-actin network are specifically adapted to
regulate Hippo and Src signaling activities (Gaspar et al., in preparation).
THE EYE SELECTOR GENE DACHSHUND PROMOTES CYTOSKELETAL
REARRANGEMENT AND EXIT FROM THE FURROW STATE.
Despite the fact that epithelium architecture constrains cells in their ability to
move, they can be engaged in a large number of morphogenetic rearrangements
and adopt a different repertoire of cell shape. Actin filaments (F-actin) are major
determinant of cell shape and can form a diversity of networks with precise
mechanical and dynamic properties. Although it becomes increasingly clear that
cell shape has a critical impact on cell differentiation and tissue morphogenesis,
the role of cell architecture in these processes is far from clear.
We aimed in this project to get insight on how F-actin is regulated to promote
cell shape changes and how this impacts on tissue morphogenesis and cell differentiation.
To do so, we used the developing Drosophila eye, to investigate
the role of actin isoforms, actin regulatory proteins, eye selector genes and
signaling pathways in triggering cell shape changes required for neuronal differentiation.
Dachshund (dac), the most downstream element among the known RDGN,
encodes a nuclear protein related to the Sno/Ski protein family of proto-oncogenes.
We found that Dac promotes cell shape required for proper differentiation
of the retina. Our results argue that one function of the Dac nuclear
factor is to regulate cytoskeletal rearrangement required to exit the furrow
state thereby controlling the timing of differentiation (Brás-Pereira et al., in
preparation).
THE RETINAL DETERMINATION GENE DACHSHUND ENSURES PATTERNED CELL
PROLIFERATION BY LIMITING YORKIE FUNCTION
Recent studies have demonstrated an important role for the human Dac homolog
DACH1 in tumorigenesis. We showed that in the Drosophila eye imaginal
disc, Dac suppresses inappropriate tissue growth by inhibiting Yorkie activity,
which mediates Hippo signaling. Since Dac interacts physically with the Yorkiebinding
partner Homothorax, our findings indicate that Dac is recruited to the
promoter of Yorkie targets to inactivate proliferation and survival genes (Brás-
Pereira et al., in preparation).
HOMEOSTASIS OF THE DROSOPHILA ADULT RETINA BY CAPPING PROTEIN
AND THE HIPPO PATHWAY
The conserved Hippo signaling pathway regulates multiple cellular events, including
tissue growth, cell fate decision and neuronal homeostasis. We provide
evidence that the actin cytoskeleton promotes neuronal homeostasis of the
adult Drosophila retina through misregulation of the Hippo pathway. We propose
a model by which F-actin dynamics is involved in all processes that require
the activity of the core Hippo kinase module (Brás-Pereira et al., 2011).
IGC ANNUAL REPORT ‘11
RESEARCH GROUPS
44