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Poster Full Abstracts - Stem Cells
Poster board number is above title. The first author is the presenter
357
844A
The role of the adiponectin receptor homolog in Drosophila melanogaster oogenesis.
Kaitlin Laws
1
, Leesa LaFever
2
, Daniela Drummond-Barbosa
1,3
. 1)
Department of Biochemistry and Molecular Biology, Division of Reproductive Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD;
2) Division of Experimental Hematology and Cancer Biology, Children's Hospital Research Foundation, University of Cincinnati, Cincinnati, OH; 3)
Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
The ability of a stem cell to sense and respond appropriately to systemic cues is integral for the coordination of its behavior with whole organism
physiology. The
Drosophila melanogaster
ovary is a stem cell-based system that rapidly responds to the diet of the organism through hormonal and local
nutrient-sensing pathways. Previous work in our lab demonstrated that
Drosophila
ovarian germline stem cells (GSCs) require several nutrient-sensing
pathways, including insulin signaling directly for their proliferation and indirectly for their maintenance. It is unclear, however, whether adipose tissue
secreted proteins play a role in the modulation of stem cell activity. In mammals, the adipose tissue secretes adipokines that modulate organismal
metabolism and homeostasis. The adipokine adiponectin is of particular interest because of its well-described role as an insulin-sensitizing agent. Although
there is no obvious
Drosophila
homolog of adiponectin based on primary sequence, a homolog of the adiponectin receptor,
CG5315
, has been identified. We
have generated a null
CG5315
mutant allele and obtained
CG5315
hairpin lines for RNAi, and are in the process of analyzing the roles of
CG5315
during
Drosophila
oogenesis. These studies will provide us with a more complete view of how stem cells respond to various diet-dependent cues to coordinate
tissue behavior with the physiology of the organism.
845B
Elucidating the mechanism of asymmetric division within the epithelial follicle stem cell niche.
Angela Castanieto, Todd Nystul. University of
California San Francisco, San Francisco, CA.
Adult stem cells are maintained through the action of a specialized microenvironment, or niche, that facilitates asymmetric division. Detailed studies of the
Drosophila male and female germline stem cell niches have provided valuable insight into the mechanism by which asymmetric stem cell division occurs in
vivo. However, less is known about somatic stem cell niches in Drosophila and it is unclear whether somatic stem cells use a similar mechanism to self-
renew. We used the epithelial follicle stem cells (FSCs) in the Drosophila ovary as a model for understanding the mechanism of asymmetric division in an
epithelial stem cell. Precisely two follicle stem cells per germarium reside in defined locations against the basement membrane at the anterior edge of the
tissue. Loss of components of the Bone morphogenetic protein (Bmp) pathway from FSCs causes rapid loss from the niche, indicating that this pathway is
required for self-renewal (Kirilly et al, 2005). We found that loss of components of the Epidermal Growth Factor Receptor (EGFR) pathway causes early
follicle cell differentiation defects. These findings have led us to investigate the involvement of the Bmp and EGFR pathways in the regulatory mechanism
of FSC asymmetric division. Here we present our data in support of a model in which Bmp and EGF signaling promote asymmetric FSC division through
regulation of follicle cell differentiation and cell polarity. These findings will further our understanding of asymmetric division in an epithelial niche.
846C
Apontic controls somatic stem cell numbers in the testis by inhibiting the JAK/STAT signaling pathway.
Michelle Starz-Gaiano, Archana Murali,
Kathryn Bus. Biological Sciences, University of Maryland Baltimore County, Baltimore, MD.
The molecular mechanisms governing adult stem cell maintenance within a microenvironment are incompletely understood, and are a central issue in
regenerative biology. The Drosophila testis provides an ideal context for examining the genetic and molecular signals that balance stem cell self-renewal and
differentiation. In the testis, germ line stem cells (GSCs) and somatic cyst stem cells (CySCs) are maintained by their association with niche cells, called the
hub. Several laboratories have shown that activation of the Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway is
necessary maintaining both types of stem cells. We have found that Apontic (APT), a transcription factor and STAT signaling feedback inhibitor, is highly
expressed in the somatic cells of the testis. When
apt
is overexpressed in the soma, there are fewer CySCs, while overexpression in the germ line has no
effect. In
apt
loss of function mutants, we observe more Zfh-1-positive CySCs, and an expanded domain of GSCs. The
apt
mutant phenotype is distinct from
those due to mutations in other STAT targets or regulators, such as
socs36e
. In ovaries,
apt
mutant cells display altered adhesion and morphological
properties, and parallel changes may explain delayed CySCs differentiation in the testis. Thus, additional CySCs in
apt
mutants may permit GSCs self-
renewal by acting as a secondary niche or altering the architecture of the microenvironment. We propose that APT acts cell-autonomously in a genetic circuit
to maintain CySC by restricting STAT signaling and Zfh-1 expression to cells in the niche. It may also act non-autonomously to organize the GSCs within
the distal tip of the testis. This suggests a complex interplay between different types of stem cells maintain the appropriate number of each near the niche.
847A
Trio regulates midgut stem cell proliferation and differentiation.
Longze Zhang, Heinrich Jasper. Biology Department, University of Rochester,
Rochester, NY.
Somatic stem cells are critical for tissue renewal and maintenance. In recent years, studies on Drosophila midgut stem cells have provided important new
insights into the regulation of stem cell proliferation and differentiation, as well as the role of stem cells in maintaining tissue homeostasis. In this study, we
have identified a function for the RhoGEF protein Trio as a critical regulator of stem cell activity and function in the Drosophila intestine. Trio was
identified in a screen for genes expressed specifically in the intestinal stem cell (ISC) lineage. It is expressed in both ISCs and the immediate daughter cell,
the enteroblast (EB), but not in other cell types of the posterior midgut. Using MARCM, as well as ISC and EB-specific Gal4 drivers, we found that trio has
distinct roles in ISCs and EBs. In stem cells, trio controls proliferation, being both sufficient and required for ISC division. At the same time, our data
suggest that trio is required to sustain Delta expression in ISCs. In EBs, trio regulates cell fate. Trio has been implicated in N signal transduction in neurons,
mediating non-canonical signaling events downstream of the N receptor. We are currently testing whether Trio acts in a similar fashion in EBs, thus
regulating differentiation of EBs into ECs and/or enteroendocrine cells. As trio is conserved from Caenorhabditis elegans to humans, our study has the
potential of providing new insight into the regulation of stem cell function in both invertebrates and vertebrates, including humans.