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Poster Full Abstracts - Pattern Formation
Poster board number is above title. The first author is the presenter
322
University, Camden, NJ, 08102, USA; 3) Department of Computer Science, Rutgers University, Camden, NJ 08102, USA; 4) Department of Chemical and
Biological Engineering, Lewis Sigler Institute for Integrative Genomics, Carl Icahn Laboratory, Princeton University, Princeton, NJ 08544, USA.
The bone morphogenetic protein (BMP) signaling pathway is a conserved regulator of cellular and developmental processes in animals. The mechanisms
underlying BMP signaling activation differ among tissues and mostly reflect changes in pathway components. BMP signaling is one of the major pathways
responsible for patterning the
Drosophila
eggshell, a complex structure derived from a layer of follicle cells (FCs) surrounding the developing oocyte.
Activation of BMP signaling in the FCs is dynamic; initially, signaling is along the anterior-posterior (A/P) axis. Later, signaling acquires dorsal-vernal
(D/V) polarity. These dynamics are regulated by changes in the expression pattern of the type I BMP receptor
thickveins
(
tkv
). We found that signaling
dynamics and
tkv
patterning are highly correlated in the FCs of multiple
Drosophila
species. In addition, we showed that signaling patterns are spatially
different among species. Using a mathematical model to simulate the dynamics and differences of BMP signaling in numerous species, we predicted that
qualitative and quantitative changes in a receptor can lead to differences in the spatial pattern of BMP signaling. We tested these predications experimentally
in three different
Drosophila
species and through genetic perturbations. Based on the results, we concluded that changes in
tkv
patterning are responsible for
the differences in the patterns of BMP signaling activation found in the FCs of
Drosophila
species.
713B
Patterning potential of the terminal system in segmentation of the
Drosophila
embryo.
Yoosik Kim, Kate M. Fitzgerald, Stanislav Y. Shvartsman.
Department of Chemical and Biological Engineering and Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
Segmentation of the
Drosophila
embryo is initiated by four maternal signals. Anteriorly localized Bicoid controls gap genes along the anteroposterior (AP)
axis by directly activating them in the anterior half of the embryo and also by repressing translation of Caudal, generating the posterior-to-anterior gradient
of the protein. Nanos is localized at the posterior pole and regulates gap genes by repressing translation of maternal
hunchback
. The non-segmented termini
are patterned by localized activation of the Mitogen-Activated Protein Kinase (MAPK) pathway. Together, these four systems control gap genes at
appropriate positions along the AP axis, which then establish multidomain expression patterns of pair-rule genes. Removal of the terminal signal from the
wild-type embryo affects only the terminal regions, suggesting that it is responsible for patterning of only a small fraction of the AP axis. Here we
demonstrate that, in absence of anterior and posterior signals, the terminal system can segment the AP axis on its own. Using quantitative imaging and
modeling approaches, we analyzed the expression of six gap genes (
hunchback
,
giant
,
knirps
,
Kruppel
,
tailless
, and
huckebein
) and one pair-rule gene (
eve
)
in this mutant background. We found that this embryo develops a symmetric cuticle pattern along the AP axis, with two segments in each half. We propose a
mathematical model that can explain both this cuticle pattern and the underlying patterns of gene expression.
714C
Description and visualization of motor neuron morphology in three dimensions.
Prateep Mukherjee
1
, Jennifer Brazill
2
, Michael D. Kim
2
, Gavriil
Tsechpenakis
1
. 1) Computer and Information Science, Indiana University-Purdue University Indianapolis, IN; 2) Department of Molecular and Cellular
Pharmacology, University of Miami School of Medicine, FL.
Dendrites are fundamental determinants of neuronal function and the morphological properties of dendrites have a direct influence on the types and
numbers of synaptic inputs a neuron receives, and consequently, the way in which a neuron integrates and processes these impinging signals. In vertebrates,
motor neurons that target different muscles establish distinct dendrite arborization patterns within the spinal cord and respond to sensory stimulation with
different latencies. Consequently, the selectivity of synaptic input is largely determined by the differential orientation and positioning of motor neuron
dendrites in the spinal cord. Although understanding how motor neurons achieve their final dendritic morphologies remains an important and understudied
problem in motor circuit formation, the overwhelming number and complexity of motor neurons and connections in the vertebrate spinal cord remains a
critical barrier in addressing this problem. In this work, we use a hybrid model- and appearance-based Computer Vision approach to automatically segment
neuron volumes in three dimensions and simultaneously partition them into three distinct compartments, namely axon, soma and dendrites, from z-series
image stacks of single-neuron MARCM clones. This morphology estimation yields a compact numerical description of each individual motor neuron, which
allows for the unbiased comprehensive analysis of mutations that specifically alter the dendritic arborization patterns of distinct motor neuron subtypes. Our
study provides important insight into how different motor neuron subtypes organize and pattern their dendrites in the CNS and will reveal novel molecular
mechanisms that control synaptic connectivity in the Drosophila motor circuit.
715A
Using a variable expressivity mutant to study pair-rule gene regulation via evolution
in silico
.
Alexander V. Spirov
1,2
, Francisco J.P. Lopes
3
, David M.
Holloway
4
. 1) The I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, St-Petersburg, Russia; 2) Computer Science and CEWIT, State
Univ New York, Stony Brook, NY; 3) Instituto de Biofisica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; 4) Mathematics, British
Columbia Institute of Technology, Burnaby, BC, Canada.
bcd
K57R
flies are defective in the cooperative binding of the Bicoid (Bcd) ligand (Lebrecht et al., 2005), and are a way to study the stochastic aspects of
gene penetrance and expressivity at the maternal level (Lopes et al., 2008; Holloway et al., 2011).
bcd
K57R
flies display a wide range of anterior shifts in
expression of the downstream target
hunchback
(
hb
), from quite weak to very strong (nearly equal to those seen in
bcd
-/- or
stau
mutants). Even-skipped
(Eve) pair-rule patterning in the
bcd
K57R
background also shows a range of discrete outcomes, from nearly WT, to mild, to severe cases reminiscent of
bcd
E3
embryos. We are modeling these downstream effects at the cis-regulatory module (CRM) level (Spirov & Holloway, 2010; 2012), the simplest biologically
reasonable level at which to treat pair-rule patterning, since each of the (usual) seven pair-rule stripes (or pair of stripes) is under the control of autonomous
stripe-specific regulatory elements. The known mapping of regulator binding sites is entered into the model, and we find the strengths of these interactions
through a selective Evolutionary Computation process. These computational experiments allow us to understand how CRM structure and binding strengths
combine to both read out pair-rule patterns and buffer against upstream variability in maternal factors and
hb
. Our modeling has found complex patterns that
recapitulate the variable anterior shifting seen in
bcd
K57R
. In these solutions, disturbed pair-rule patterns are in part due to
hb
shifts (also seen
experimentally). Our results demonstrate how maternal variability (from a mutant condition) can be amplified, through the gap level, down to pair-rule
expression.