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Abstracts - Society for Developmental Biology

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45<br />

Elevated nuclear translocation of NF-κB was also discovered in lungs from transgenic mice. An evaluation of genes<br />

regulated by NF-κB demonstrated elevated expression of Fas ligand, suggesting increased activity of the Fas-mediated<br />

signaling pathway in which ligand-receptor interaction triggers cell death. These data provide evidence that RAGE<br />

expression must be tightly regulated during organogenesis and that RAGE signaling during branching morphogenesis may<br />

provide insight into the progression of developmental lung anomalies including bronchopulmonary dysplasia.<br />

Program/Abstract # 137<br />

Glycosaminoglycan biosynthesis is required non-cell-autonomously <strong>for</strong> correct patterning of the dorso-anterior<br />

Drosophila eggshell by the Epidermal Growth Factor Receptor ligand Gurken<br />

LeMosy, Ellen K.; Neiswender, Hannah, Georgia Health Sciences University, Augusta, United States<br />

Graded EGF-R signaling within the follicle cell epithelium occurs in response to a germline-derived ligand, Gurken (Grk),<br />

secreted dorso-anteriorly near the position of the oocyte nucleus. High Grk levels specify dorsal midline, intermediate<br />

levels specify position of the dorsal appendages, and lowest levels allow expression of Pipe ventrally to later define the<br />

dorsoventral axis of the embryo. Prior studies by Li-Mei Pai’s lab showed that over-expression of Dally-like, a membranelinked<br />

heparan sulfate proteoglycan (HSPG), results in a shallower extracellular gradient ofGrk and a reduced gap between<br />

the dorsal appendages, indicating loss of high-Grk domain, while the Pai lab and David Stein’s lab report that Fringe<br />

Connection (frc) and Sulfateless (sfl), enzymes involved in HS synthesis and sulfation, respectively, are not required <strong>for</strong><br />

eggshell patterning. We examined strong mutant alleles of protein O-xylosyl transferase (oxt), the first and rate-limiting<br />

enzyme acting in glycosaminoglycan (GAG) synthesis. Egg chambers containing anterior or complete oxt-mutant follicle<br />

cell clones show increases in size of the dorsal gap between dorsal appendage primordia from 3-4 cells wide to up to 6-7<br />

cells wide, while small clones do not exhibit cell-autonomous changes in fate. These findings suggest loss of follicle cellderived<br />

GAGs is associated with expansion of the high-Grk domain. The most notable change in Grk distribution is its<br />

ectopic presence within germline vesicles in affected egg chambers. One possibility suggested by this data is that there is<br />

reduced uptake and degradation of Grk by follicle cells when it is not bound to GAGs, leading to increased EGF-R<br />

signaling and perhaps alternative uptake into the oocyte.<br />

Program/Abstract # 138<br />

Mirror and Paxillin act downstream of Tramtrack69 to regulate tube morphogenesis in the Drosophila ovary<br />

Peters, Nathaniel C., University of Washington Genome Sciences, United States<br />

Epithelial tubes are essential <strong>for</strong> organ and tissue function, and faithful tubulogenesis requires precise orchestration of cell<br />

signaling, shape change, migration, and adhesion. Epithelial follicle cells in the Drosophila ovary undergo morphogenesis<br />

to <strong>for</strong>m a pair of tubes, the apical lumens of which act as molds <strong>for</strong> the egg shell respiratory filaments, or dorsal<br />

appendages (DAs); this system is a robust and accessible model <strong>for</strong> studying epithelial tube patterning, <strong>for</strong>mation, and<br />

expansion. The Tramtrack69 (TTK69) transcription factor controls DA lumen volume by regulating apical surface area<br />

and tube expansion; the twin peaks mutant reduces TTK69 levels specifically late in oogenesis, inhibiting tube expansion<br />

and stunting the DAs. Microarray analysis of wild type and twin peaks ovaries, followed by in situ validation of candidates,<br />

identified mirror and paxillin as TTK69 targets. mirror encodes a homeodomain protein that patterns the epithelium prior<br />

to DA tubulogenesis, but post-patterning RNAi-knockdown disrupted DA tube expansion, indicating that mirror may have<br />

a novel role in DA tubulogenesis. paxillin expression is highest in the DA tube cells just prior to tube expansion, and<br />

RNAi-knockdown of paxillin resulted in DA tube defects. We are now determining whether Paxillin, a scaffolding protein,<br />

interacts with Integrin-based cell adhesions, JNK signaling, and/or GPCR signaling, all of which are required <strong>for</strong> DA<br />

tubulogenesis, and whether TTK69 regulates paxillin via a mirror-dependent pathway. Further characterization of TTK69<br />

targets, such as paxillin and mirror, will help illuminate the network of transcription factors, signaling pathways, and<br />

cytoskeletal regulators required <strong>for</strong> epithelial tube morphogenesis.<br />

Program/Abstract # 139<br />

ErbB signaling within Schwann cells controls quiescence of zebrafish lateral line progenitor cells through<br />

regulation of Wnt and FGF signaling.<br />

Lush, Mark E., Stowers Institute <strong>for</strong> Medical Research Research, United States; Piotrowski, Tatjana (Stowers Institute <strong>for</strong><br />

Medical Research, Kansas City, MO, United States)<br />

The Zebrafish lateral line is a mechanosensory system consisting of neuromasts containing support cells and sensory hair<br />

cells. The <strong>for</strong>mation of the lateral line has proven an excellent model <strong>for</strong> the study of developmental events, such as<br />

collective cell migration. Here we show that it is also a unique model to study stem cell biology. Previous work from our<br />

laboratory revealed a role <strong>for</strong> glia in negatively regulating proliferation and differentiation of lateral line stem cells.<br />

Mutations in erbb2, erbb3b and nrg1-3 have increased neuromast numbers. We show by transplantation experiments and

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