Congress Abstracts - Society for Developmental Biology

characterization of Pkp3 in early vertebrate embryos of Xenopus laevis. Pkp3 knock-down phenotypes include hyposensitivity to
touch and altered PNS-staining, showing that Pkp3 is required in amphibian development. At the molecular level, I will present a
novel interaction resolved between Pkp3 and ETV1, an ETS-family transcription factor, and preliminarily on Wnt-pathway regulation
of Pkp3 stability / activity. My goal is to deepen our cellular and developmental understanding of Pkp3, especially with regards to its
poorly understood roles in the nucleus. This will provide the basis to ultimately address if Pkp3’s role in gene regulation is linked to
its roles at desmosomal cell-cell junctions.
Program/Abstract # 320
Bidirectional Notch-Delta signaling in Nematostella vectensis suggests that Delta activation is a key component to this
signaling pathway in animals.
Layden, Michael; Martindale, Mark (Whitney Laboratory for Marine Bioscience, USA)
Notch signaling is redeployed throughout animal development to govern cell fate decisions in developing tissues. Traditionally, Notch
signaling has been described as one directional, and it is initiated by the Delta ligand on one cell interacting with the Notch receptor on
the adjacent cell. Notch and Delta are single pass transmembrane proteins that undergo a proteolytic cleavage that releases the
intracellular domain (ICD) of upon activation. However, only function of the Notch ICD has been extensively studied. The Notch ICD
regulates gene expression and generally promotes an undifferentiated cell fate, which is often associated with maintaining proliferative
potential. Cell culture and limited genetic studies suggest that the Delta ICD also undergoes nuclear translocation and that Delta
promotes cell differentiation and loss of proliferation. We characterized Notch signaling during neurogenesis in Nematostella. We
show that Delta activates Notch signaling and Notch activation inhibits differentiated neural gene expression. Currently, our data
suggests that Notch does not promote cell proliferation. Conversely, Delta inhibits cell proliferation and increases differentiated neural
gene expression. We also demonstrate that the Delta ICD localizes to the nucleus and is likely to regulate gene expression. Taken
together our data supports the mounting evidence that Notch signaling is more likely to be bidirectional Notch-Delta signaling. The
role of Notch-Delta signaling in regulating the delicate balance of growth and differentiation and the link between defects in Notch-
Delta signaling various forms of cancer supports future work focused on understanding the Delta signaling component.
Program/Abstract # 321
Thermal stability regulates fibroblast growth factor signaling
Krejci, Pavel; Vesela, Iva (Masaryk University, Czech Republic); Buchtova, Marcela; Zajickova, Renata (University of Veterinary
and Pharmaceutical Sciences, Czech Republic); Zakrzewska, Malgorzata (University of Wroclaw, Poland); Wiedlocha, Antoni
(University of Oslo, Norway); Martin, Jorge (Cedars-Sinai Medical Center, USA)
The fibroblast growth factor (FGF) system represents one of the fundamental tools of cell communication. Eighteen FGFs act as tissue
growth factors or metabolic hormones to regulate many important processes throughout development, life, and disease. We report that
biological activity of FGF1, FGF4, FGF5, FGF6, FGF8, FGF9, FGF16-18, and FGF20 is severely limited in vitro and in vivo,
manifested as failure to activate downstream FGF-receptor (FGFR) signaling over a long period of time, and to influence specific cell
behavior. This phenotype is not caused by FGFR specificity or the absence of appropriate low affinity FGF co-receptors (the heparan
sulfate proteoglycans) at the cell surface. Instead, failure to signal stems from thermal instability in at least 10 different members of
FGF family. We further demonstrate that stabilization via exogenous heparin binding, introduction of stabilizing mutations or
lowering the cell cultivation temperature rescues the biological activity of unstable FGFs in both in vitro and in vivo environments.
Our data suggest that limited thermal stability may regulate biological activity of extracellular signaling molecules.
Program/Abstract # 322
Trachea-derived Dpp controls adult midgut homeostasis in Drosophila
Lin, Xinhua; Zhouhua, Li; Zhang, Yan; Han, Lili; Shi, Lai (Chinese Academy of Sciences, China)
Homeostasis in adult tissues is maintained by resident stem cells and their progeny. Little is known about the regulation of tissue
homeostasis by organ-organ interaction. With the use of the Drosophila model, we demonstrate that trachea-derived Decapentaplegic
(Dpp), the main BMP ligand in Drosophila, is essential for adult midgut homeostasis. We show that Dpp signaling is primarily
activated in enterocytes (ECs). Depletion of Dpp signaling in ECs results in excess amounts of intestinal stem cell (ISC)-like cells and
their progeny, similar to the human juvenile polyposis (JP) syndrome harboring mutations in BMP pathway genes. Importantly, we
find that Dpp is expressed specifically in tracheal cells. Tracheal cells reach the intestinal cells through the visceral muscles (VMs).
We show that depletion of dpp expression in tracheal cells phenocopies the Dpp loss-of-function defects in ECs. Finally, we
demonstrate that loss of Dpp signaling in EC cells causes apoptosis and elevated JNK signal activity while ectopic expression of antiapoptotic
p35 or Diap1 was able to greatly suppress the defects. Our data demonstrate that the Drosophila trachea not only exchanges
air for bodily needs, but also produces a Dpp morphogen essential for neighboring tissue homeostasis. On the basis of our
observations, we propose that trachea-derived Dpp activates Dpp signaling in ECs to protect ECs from cell death and counteract
environmental insults. Stabilized ECs in turn restrict ISCs from excessive proliferation, thus maintaining intestinal homeostasis. The
identification of the trachea as the signal source for midgut homeostasis will provide important insight into our understanding of the
mechanisms of tissue homeostasis control by inter-organ communication.
The identification of the trachea as the signal source for midgut homeostasis will provide important insight into our understanding of
the mechanisms of tissue homeostasis control by inter-organ communication.
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