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Abstracts - Society for Developmental Biology

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Program/Abstract # 74<br />

A developmental biologist’s <strong>for</strong>ay into science policy<br />

Grant, Kelly A., Gannon University <strong>Biology</strong>, Erie, United States<br />

The American Association <strong>for</strong> the Advancement of Science (AAAS) offers science policy fellowships to scientists of all<br />

disciplines. The fellowship promotes mutually beneficial relationships where scientists share their expertise and analytic<br />

skills with Congressional offices and executive branch agencies while scientist learn about policy. As a developmental<br />

biologist my policy interests focused on the effects of environmental pollutants on development, especially exposure to<br />

endocrine disruptors. Based on these interests, I selected an office at the EPA that offered me the opportunity to evaluate<br />

toxicological profiles of chemicals and devise plans to reduce the use of chemicals of concern. In my two years at the EPA,<br />

I developed the strategy to reduce human and environmental exposure to bisphenol A (BPA), which included an initiative<br />

to find safer replacements to BPA in thermal paper receipts. I also worked on programs to reduce the release of<br />

nonylphenol to the environment. Nonylphenol (aka Triton X-100) is roughly 1000xs more estrogenic than BPA and is<br />

recalcitrant to biodegradation. Reducing the environmental releases of these chemicals will hopefully ameliorate conditions<br />

leading to the feminization of fish, occurring in many lakes and rivers. During my fellowship, I learned about policy<br />

making, gained experience communicating to non-biologists, and applied knowledge of developmental biology to<br />

environmental policies. I interfaced with toxicologist to develop more meaningful assays to better capture critical stages in<br />

development and/or disruption of signal transduction pathways. Finally, the work was exceptionally rewarding because it<br />

created concrete, real-world benefits. The poster will discuss my projects in more detail and I will have in<strong>for</strong>mation about<br />

the fellowship.<br />

Program/Abstract #75<br />

Dynamic filopodia transmit lont-range Shh signaling during tissue patterning.<br />

Barna, Maria; Martin, Esther Llagostera; Sanders, Timothy, UC San Francisco, United States<br />

The movement of key signaling proteins within tissues and organs is a central feature of metazoan development that must<br />

be exquisitely spatially controlled. How this is achieved at a cellular level remains poorly understood. Here we constructed<br />

a robust, state-of-the-art imaging system that allows <strong>for</strong> visualization of signaling at single cell resolution under<br />

endogenous spatial and temporal control within living vertebrate embryos. Through this imaging approach, we identified<br />

that genetically defined populations of mesenchymal cells involved in Sonic Hedgehog (Shh) signaling within the<br />

vertebrate limb bud possess a novel specialized class of actin-based filopodia spanning several cell diameters that have not<br />

been previously described. By imaging Shh responding cells in real time, we visualized an exquisite distribution and colocalization<br />

of the Shh co-receptors to discrete micro-domains along the membrane of these filopodia extensions,<br />

suggesting a functional role in facilitating long-range signaling. We there<strong>for</strong>e developed a tightly regulated expression<br />

system directed by the Shh limb-specific enhancer element to visualize Shh production in vivo. Remarkably, imaging Shh<br />

ligand itself revealed that it is normally produced in the <strong>for</strong>m ofa particle that dynamically moves along filopodia<br />

extensions and accumulates at their tips, which make stabilized contacts with responding cells that contain Shh coreceptors.<br />

Strikingly, these stabilized interactions are associated with a dramatic accumulation of Shh to the primary cilium<br />

of responding cells and activation of the pathway. To our knowledge, this is the first in vivo demonstration of Shh ligand<br />

production and movement. These findings strongly suggest that contact mediated release propagated by specialized<br />

filopodia contributes to the delivery and activation of Shh signaling at a distance. Together, these studies identify a new<br />

mode of communication between cells that extends our understanding of long-range signaling during vertebrate tissue<br />

patterning.<br />

Program/Abstract # 76<br />

Characterization of a Wls knockdown in the developing chick spinal chord<br />

Allen, Sean, San Francisco State University, United States<br />

The Wnt signaling pathway contributes to the regulation of important developmental and cellular events, such as cell<br />

survival, proliferation, and specification. Within vertebrates, one of the best-characterized examples of a Wnt gradient is<br />

found in the developing spinal cord. There, dorsally expressed Wnts <strong>for</strong>m a dorsal to ventral gradient of proliferation and<br />

neuronal specification. For Wnts to function properly, they must first be secreted from Wnt-producing cells. Wntless<br />

(Wls), a transmembrane protein, is necessary <strong>for</strong> the secretion of all known Wnt family members invertebrates. Knockout<br />

of Wls in the mouse model system causes early embryonic lethality that coincides with the timing of the first known<br />

requirement <strong>for</strong> Wnt signaling. The goal of this project was to determine the role of Wls in Wnt gradient <strong>for</strong>mation in the<br />

chick spinal cord. Specifically, we hypothesized that loss of Wls would disrupt the Wnt gradient and thereby cause defects<br />

in survival, proliferation, and patterning. To test this hypothesis, electroporation was used to achieve a transient siRNAmediated<br />

knockdown of Wls. Transverse sections were analyzed <strong>for</strong> morphological changes, the most noticeable of which

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