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Congress Abstracts - Society for Developmental Biology

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Program/Abstract # 48<br />

Modeling regulatory systems <strong>for</strong> sea urchin development<br />

Isabelle Peter, Eric Davidson (Caltech, USA)<br />

The <strong>for</strong>mation of distinct cell fate specification domains occurs by means of spatial control of gene expression. At the system level,<br />

gene regulatory network (GRN) models attempt to incorporate the complete gene regulatory apparatus which determines a specific<br />

developmental process. Yet as these network models include an increasing number of regulatory genes, the outcome of the regulatory<br />

interactions between them becomes less easily comprehensible. The sea urchin endomesoderm GRN consists of about 50 regulatory<br />

genes and determines the <strong>for</strong>mation of at least five different gene expression domains be<strong>for</strong>e the onset of gastrulation. A recently<br />

developed Boolean model demonstrates that the experimentally established regulatory interactions which constitute the<br />

endomesoderm GRN model are indeed largely sufficient to reconstruct the spatial and temporal regulatory gene expression patterns<br />

observed during the first thirty hours of sea urchin development. Furthermore, perturbation of the Boolean model accurately predicted<br />

the outcome of experimental perturbation. The Boolean model thus shows that GRN models are in principle sufficient to explain<br />

progressive regulatory gene expression during development and it contributes to the <strong>for</strong>malization of regulatory processes. The<br />

insights gained from this analysis are now being applied to a much more complex process of post-gastrular organogenesis, the<br />

<strong>for</strong>mation of the embryonic gut.<br />

Program/Abstract # 49<br />

A gene regulatory network <strong>for</strong> endomesodermal specification in a basal deuterostome.<br />

Veronica Frances Hinman, Brenna McMauley (Carnegie Mellon, USA)<br />

A central pursuit in developmental biology is to understand how maternal processes can generate an embryo with molecularly distinct<br />

cell populations. A causal explanation <strong>for</strong> this requires a comprehensive gene regulatory network (GRN) model that can explain how<br />

genes are expressed at exactly the right time and in the right cells. We will discuss our recent work that describes the GRN <strong>for</strong> one of<br />

the most important events in early development, the specification and segregation endoderm and mesoderm, using the sea star, Patiria<br />

miniata, as our model system . Sea stars are a class of Echinoderms that are considered to represent the basal mode of development<br />

of this phylum and possibly of all deuterostomes. The simplicity of sea star early development allows us to provide a detailed<br />

explanation of endomesderm specification. Sea stars undergo equal cleavage and generate a holoblastula of only several hundred cells.<br />

Endomesoderm fated cells <strong>for</strong>m at the vegetal pole of the early embryo. Later mesoderm fated cells will segregate as central<br />

population surrounded by a torus of endoderm. We show that this process is regulated by a spatio temporal gradient of nuclear β<br />

catenin. A maternally controlled transcriptional factor based GRN additionally provides timing control <strong>for</strong> gene activation to ensure a<br />

robust response to nuclear β catenin. We will also discuss how these GRN topologies can evolve by altering the β catenin gradient<br />

and other signaling pathways.<br />

Program/Abstract # 50<br />

Gene regulatory network of neural crest development<br />

Maneeshi Prasad, (Northwestern, USA)<br />

The Neural Crest (NC) is an embryonic stem cell population that is induced at the neural plate border in vertebrates and later<br />

emigrates from the dorsal aspect of the developing neural tube, migrate extensively, and give rise to a large and diverse group of cell<br />

types. A network of signaling pathways and transcription factors <strong>for</strong>m the neural crest gene regulatory network (NC-GRN) that<br />

regulates the induction, specification and migration of NC. These signaling gradients from the neural and non-neural ectoderm, and<br />

mesoderm in the <strong>for</strong>m of Wnt and BMP antagonists induce the expression of early neural crest specifiers, Snail, Twist and Sox9. But<br />

not much is known about the downstream targets of these neural crest specifiers and their role during different stages of NC<br />

development. However, the reiterative use of these factors during different stages of neural crest development suggests their role in<br />

regulating different target genes in a temporally controlled manner. To better understand their role in NC-GRN it is essential to<br />

decipher their targets during different stages of NC development. Using genome wide approaches such as ChIP-Seq and RNA-Seq, we<br />

have identified new putative regulatory targets of these neural crest specifiers during premigratory stages of neural crest development<br />

in Xenopus laevis embryos. These targets include genes involved in regulating EMT as well as maintaining stem cell state. We<br />

confirmed the presence of known targets of these factors and also new putative targets that are involved in induction and migration<br />

stages of NC development. These Sox9 and Twist targets will provide more insights into the role of these NC specifiers during<br />

different stages of NC development and also elaborate their role in NC-GRN.<br />

Program/Abstract # 51<br />

The phosphorylation state of Drosophila Mad determines its choice between BMP and Wingless signaling<br />

Edward Eivers, Marlyn Rios, Abigail Aleman, Daniel Lee, Matthew Juarez, Keristineh Vartanpour (CSU Los Angeles, USA)<br />

Bone morphogenetic proteins (BMPs) and Wnts are growth factors that are known to regulate a broad range of cellular events such as<br />

stem cell maintenance, cell differentiation and organogenesis, while dysfunctional signaling of either pathway can result in severe<br />

developmental abnormalities. Here we describe a new molecular mechanism by which the phosphorylation state of the transcription<br />

factor Mad determines its ability to transduce either BMP or Wingless (a Wnt ligand) signals in Drosophila cells. Previously, Mad was<br />

thought to function in gene transcription only when phosphorylated by the BMP receptor. We now demonstrate that Mad is required<br />

<strong>for</strong> canonical Wingless signaling specifically when in an unphosphorylated state, by <strong>for</strong>ming a Mad-Pangolin-Armadillo Wnt<br />

15

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