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Poster Full Abstracts - Cell Biology and Signal Transduction
Poster board number is above title. The first author is the presenter
176
157A
Regulation of epithelial polarity by the E3 ubiquitin ligase Neuralized and the Bearded inhibitors in Drosophila.
soline chanet, françois schweiguth.
Inst Pasteur - CNRS URA 2578, Paris.
Understanding how epithelial polarity is established and regulated during tissue morphogenesis is a major issue. Here, we identify a novel regulatory
mechanism important for mesoderm invagination, germ-band extension and trans-epithelial migration in the Drosophila embryo. This mechanism involves
the inhibition of the conserved E3 ubiquitin ligase Neuralized by the proteins of the Bearded family. First, Bearded mutant embryos displayed a loss of
epithelial polarity associated with an early loss of the apical domain. Bearded regulated epithelial polarity by antagonizing neuralized. Second, repression of
Bearded gene expression by Snail was required for the Snail-dependent disassembly of Adherens Junctions in the mesoderm. Third, neuralized was strictly
required to promote the down-regulation of the apical domain in the midgut epithelium and to facilitate the trans-epithelial migration of primordial germ
cells across this epithelium. This function of Neuralized was independent of its known role in Notch signalling. Thus, Neuralized has two distinct functions
in epithelial cell polarity and Notch signalling.
158B
Wild-type Planar Cell Polarity requires the spatially restricted activity of Prickle protein isoforms.
Simon Collier, Meagan Valentine, Andrea
Belalcazar. Dept Biological Sci, Marshall Univ, Huntington, WV.
Two isoforms of the Prickle protein, Pk and Sple, are active in Frizzled Planar Cell Polarity (Fz PCP) signaling during adult fly development. Loss-of-
function phenotypes reveal that the two Prickle isoforms play different roles in the development of adult PCP, and gain-of-function experiments show that
the two isoforms have different cellular activities. Both Prickle isoforms contain a PET domain and three LIM domains, but differ in their N-termini.
Specifically, the 13 N-terminal amino acids in the Pk isoform are replaced by 349 amino acids in the Sple isoform. Using the Gal4-UAS system, we have
generated flies that express just one Prickle protein isoform (either Pk or Sple) ubiquitously throughout development. We have compared the PCP of these
flies in numerous tissues including wing, abdomen, thorax, leg and eye. In most regions examined, one Prickle isoform (either Pk or Sple) confers wild-type
polarity, while the other confers an alternate polarity. Our findings suggest that wild-type PCP in the adult fly is generated using a patchwork of Fz signals
that incorporate either the Pk isoform or the Sple isoform. We refer to as the Prickle Isoform Code. We are currently attempting to correlate the spatial
restricted activity of Prickle isoforms with local signaling gradients, to try to define the underlying logic of the code.
159C
aPKC
regulates localization but not function of Numb during neuroblast asymmetric divisions.
Jill Haenfler
1
, Chaoyuan Kuang
1,2
, Cheng-Yu Lee
1,3,4,5
.
1) Program in Cell and Molecular Biology; 2) MSTP; 3) Dept of Cell and Dev Biology; 4) Div of Mol Med & Genetics, Dept of Int Med; 5) Center for Stem
Cell Biology, Life Sciences Inst, Univ of Michigan, Ann Arbor, MI.
Cortical cell polarity regulates unequal partitioning of the cell fate determinants to functionally distinguish stem cells from progenitor cells during
asymmetric cell divisions. Whether polarity proteins specify stem/progenitor cell potential by regulating segregation and function of the fate determinants
remains unknown. The
Drosophila
larval brain contains steady populations of type I and II neuroblasts, which undergo repeated asymmetric divisions to
self-renew and to generate progenitor cells with restricted potential. Both populations of neuroblasts became aberrantly expanded in larval brains lacking the
tumor suppressor Lgl. To understand how Lgl suppresses formation of ectopic neuroblasts, we investigated their cellular origin using lineage analysis.
Surprisingly, we found the ectopic neuroblasts in
lgl
mutants arise due to a failure to maintain restricted potential in progenitor cells. In
lgl
mutants, Numb
failed to localize asymmetrically in mitotic neuroblasts and intermediate neural progenitors and increased function of
numb
or inactivation of
Notch
signaling suppressed the ectopic neuroblast phenotype. Exclusive asymmetric inheritance of Numb into the progenitor cells requires the ACBD3 binding
(AB) domain, which is also essential for Numb to suppress ectopic neuroblasts in
lgl
mutants. Although the non-phosphorylatable form of the Numb
transgenic protein at two conserved aPKC phosphorylation sites within the AB domain, serines 48 and 52, symmetrically segregated into both daughter cells,
unexpectedly, both the phosphomimetic and non-phosphorylatable form suppressed ectopic neuroblasts in
lgl
mutants, strongly suggesting that Numb can
suppress reversion of progenitor cells back into neuroblasts independently of the regulation by aPKC. We propose that Lgl antagonizes aPKC to ensure that
a critical threshold of Numb is reached in the future progenitor cells where Numb maintains restricted potential via an aPKC-independent mechanism.
160A
Functions of a helix-loop-helix transcription factor, Extramacrochaetae, in development of left-right asymmetry in the
Drosophila
embryonic
hindgut.
Ryo Hatori, Kiicrhio Taniguchi, Takashi Okumura, Naotaka Nakazawa, Reo Maeda, Kenji Matsuno. Tokyo University, Department of Biological
Science and Technology Noda, Chiba Yamazaki 2641.
Left-right asymmetrical morphogenesis is a critical aspect of many animal organogenesis. To understand the mechanisms involved in left-right
asymmetrical morphogenesis, we are using the embryonic hindgut of
Drosophila
. During development, the hindgut rotates left handedly 90 degrees and this
rotating direction genetically determined. In our genome wide genetic screen, we previously found that
DE-Cadherin
(
DE-Cad
)and
Myosin31DF
(
Myo31DF
) mutants show randomized and reverse laterality of the hindgut, respectively. More recently, we identified
extramacrochaetae
(
emc
), as a gene
involved in regulating the laterality of the embryonic hindgut.
emc
encodes a negative helix-loop-helix transcription factor involved in a diverse range of
biological processes such as cell-fate determination. Our epistatic analysis implies that Emc functions upstream of Myo31DF and
D
E-Cadherin. In wildtype
embryos,
D
E-Cadherin tended to be localized in a planar left-right asymmetrical manner at cell boundaries. However, in
emc
mutants, there was no left-right
bias in the planar localization of
D
E-Cadherin. Next, we hypothesized that this planar left right bias of
D
E-Cadherin localization might regulate left right
asymmetrical cell shape through differential cell adhesion. Indeed, the shape of epithelial cells of the hindgut were chiral with respect to the anterior-
posterior axis. This new type of cell chirality was named, planar cell chirality (PCC). PCC tended to be slanted to the left in wild-type flies, but
emc
mutants
showed no left-right bias in PCC. Moreover, our
in silico
simulation suggested that PCC is sufficient for the left-right asymmetric morphogenesis of the
hindgut. In summary, we have shown that
emc
might regulate the left-right asymmetrical cell shape of the hindgut by controlling the left-right asymmetrical
D
E-Cad distribution and adhesion.
161B