Congress Abstracts - Society for Developmental Biology

transcriptional complex. In contrast, C-terminal phosphorylation of Mad by BMP receptors directed Mad towards BMP signaling,
thereby actively competing with the function of Mad in the Wingless pathway. Our results indicate that Mad is a shared component
between two unrelated pathways and its distinct signal transduction roles in the BMP and Wnt pathways is controlled by a phosphoserine
code on Mad.
Program/Abstract # 52
Gli activators and repressors regulate distinct transcriptional responses through a common cis regulatory module that is
required for robust repression of Gremlin
Steven Vokes, Qiang Li, Jordan Lewandowski, Marian Powell, Seung Hee Cho, Jacqueline Norrie (UT Austin, USA)
Transcriptional response to the Hedgehog (Hh) pathway is mediated by Gli proteins, which function as context-dependent
transcriptional activators or repressors in the respective presence or absence of Hh pathway activation. The mechanism by which Gli
proteins activate and repress target genes is poorly understood. In an effort to understand this, we have characterized the response of a
Gli-dependent cis-regulatory module (CRM) that regulates Gremlin expression in the mammalian limb bud. Contrary to a prevailing
model, Gli repression does not modulate the domain of Gli activation-dependent enhancer activity and does not efficiently compete
with Gli activation. Instead, Gli repression is detected in regions lacking Gli activator activity where it prevents ectopic transcription
driven by additional CRMs. The Gli CRM is not individually essential for regulating Gremlin, acting as a shadow repressor that is
redundant with additional Gli-dependent CRMs. We propose a model where the properties of Gli activators and repressors are
spatially decoupled. Collectively, they regulate transcription through redundant CRMs that act as robust toggle switches to impose
Gli-dependent control over transcriptional activity.
Program/Abstract # 53
Modelling and classifying variation in butterfly wings
Filipa Alves (Gulbenkian Inst, Portugal)
The morphological diversity that can be observed on butterfly wings is an excellent example of phenotypic variation. Several butterfly
species are becoming established as laboratory model organisms, and a number of natural mutants has already been identified and
described. We are using a theoretical modelling approach to study the interplay between the biophysical mechanisms and the gene
regulatory networks underlying wing morphology and pigmentation patterning. We are especially interested in how this interplay both
generates and constrains the phenotypic variation observed within and among species. Our theoretical models are mainly focused on
formulating hypotheses and making testable predictions. The gene regulatory networks are defined by partial differential equations
and the spatial gene expression patterns are represented in 2D using finite differences methods. We are testing different possible
network topologies and candidate genes by comparing the models’ results with the experimental data available. Furthermore, as the
models’ calibration and validation are strongly dependent on quantifying and estimating the biological parameters involved, we are
also developing image analysis tools and databases, and implementing parameter optimization algorithms. Our results provide testable
hypotheses for how the observed variation on wing morphology and pigmentation patterns may depend on subtle changes on specific
biophysical parameters, opening interesting perspectives to understand the evolution of these mechanisms.
Program/Abstract # 54
Angioblast migration and vascularization of the embryonic cornea are inhibited by lens-derived Semaphorin3A signaling
Peter Lwigale, Chelsea McKenna (Rice, USA)
During eye development, neural crest cells migrate from the periocular region to form the cornea, but it is not clear whether blood
vessel precursors (angioblasts) avoid the presumptive cornea resulting its avascularity. Given that periocular angioblasts and ocular
blood vessels express neuropilin-1 (Nrp1), a receptor for both vascular endothelial growth factor (Vegf, pro-angiogenic factor) and
semaphorin3A (Sema3A, anti-angiogenic factor), we hypothesized that lens-derived Sema3A prevents angioblast migration and
vascularization of the developing cornea. We examined the expression of Vegf and Sema3A in the lens by immunohistochemistry and
quantified their mRNA by qPCR. We then blocked Sema3A signaling from the region of the presumptive cornea by lens ablation or
injection of Sema3A inhibitory peptides. We also investigated whether addition of Sema3A inhibits Vegf induced vascularization of
the cornea. Furthermore, we analyzed Nrp1(Sema-/-) mutant mice that lack Sema/Nrp1 signaling for defects in corneal avascularity.
Using Tg(tie1:H2B:eYFP) transgenic quail, we show that angioblasts do not migrate into the region of the forming cornea located
between the ectoderm and lens. Both Sema3A and Vegf are present in the lens, but the levels of Sema3A transcripts are significantly
higher than Vegf during cornea development. Inhibition of lens Sema3A resulted in ectopic angioblast migration and vascularization
of the forming cornea. Addition of Sema3A protein inhibits Vegf-induced vascularization of the cornea. We also observed ectopic
angioblasts and vasculature in corneas of Nrp1(Sema-/-) mutant embryos. Together, our results show that Sema3A signaling from the
lens plays a crucial role in establishing corneal avascularity.
Program/Abstract # 55
An E-cadherin mediated piggyback mechanism drives tissue spreading during epiboly
Miguel Concha, German Reig, Carolina Figueroa, Valeria Larenas, Steffen Hartel (U Chile, Chile)
The spreading of tissues is critical for the building and repair of organisms during morphogenesis and regeneration. One valuable
model to study this process is epiboly, whereby cells located in the upper hemisphere of a spherical blastula spread to cover the entire
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