Steroid hormone signaling synchronizes cell migration machinery, adhesion and polarity to direct collective movement.

Migratory cells - either individually or in cohesive groups - are critical for spatiotemporally regulated processes such as embryonic development and wound healing. Their dysregulation is the underlying cause of formidable health problems such as congenital abnormalities and metastatic cancers. Border cell behavior during Drosophila oogenesis provides an effective model to study temporally regulated, collective cell migration in vivo.

Mind bomb 2 promotes cell migration and epithelial structure by regulating adhesion complexes and the actin cytoskeleton.

Cell migration is essential in animal development and co-opted during metastasis and inflammatory diseases. Some cells migrate collectively, which requires them to balance epithelial characteristics such as stable cell-cell adhesions with features of motility like rapid turnover of adhesions and dynamic cytoskeletal structures. How this is regulated is not entirely clear but important to understand.

Development and Analysis of a Quantitative Mathematical Model of Bistability in the Cross Repression System Between APT and SLBO Within the JAK/STAT Signaling Pathway.

Cell migration is a key component in development, homeostasis, immune function, and pathology. It is important to understand the molecular activity that allows some cells to migrate. is a useful model system because its genes are largely conserved with humans and it is straightforward to study biologically.

Assessing the Age-Specific Phagocytic Ability of Adult Drosophila melanogaster Hemocytes using an In Vivo Phagocytosis Assay.

Phagocytosis is an essential function of the innate immune response. This process is carried out by phagocytic hemocytes whose primary function is to recognize a wide range of particles and destroy microbial pathogens. As organisms age, this process begins to decline, yet little is known about the underlying mechanisms or the genetic basis of immunosenescence.

Clustered cell migration: Modeling the model system of Drosophila border cells.

In diverse developmental contexts, certain cells must migrate to fulfill their roles. Many questions remain unanswered about the genetic and physical properties that govern cell migration. While the simplest case of a single cell moving alone has been well-studied, additional complexities arise in considering how cohorts of cells move together.

Lisinopril Preserves Physical Resilience and Extends Life Span in a Genotype-Specific Manner in Drosophila melanogaster.

Physical resiliency declines with age and comorbid conditions. In humans, angiotensin-converting enzyme (ACE) has been associated with attenuation of the decline in physical performance with age. ACE-inhibitor compounds, commonly prescribed for hypertension, often have beneficial effects on physical performance however the generality of these effects are unclear.

Drosophila Jak/STAT Signaling: Regulation and Relevance in Human Cancer and Metastasis.

Over the past three-decades, Janus kinase (Jak) and signal transducer and activator of transcription (STAT) signaling has emerged as a paradigm to understand the involvement of signal transduction in development and disease pathology. At the molecular level, cytokines and interleukins steer Jak/STAT signaling to transcriptional regulation of target genes, which are involved in cell differentiation, migration, and proliferation. Jak/STAT signaling is involved in various types of blood cell disorders and cancers in humans, and its activation is associated with carcinomas that are more invasive or likely to become metastatic.

Cytokine exocytosis and JAK/STAT activation in the ovary requires the vesicle trafficking regulator α-Snap.

How vesicle trafficking components actively contribute to regulation of paracrine signaling is unclear. We genetically uncovered a requirement for α-soluble NSF attachment protein (α-Snap) in the activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway during egg development. α-Snap, a well-conserved vesicle trafficking regulator, mediates association of N-ethylmaleimide-sensitive factor (NSF) and SNAREs to promote vesicle fusion.

A hormonal cue promotes timely follicle cell migration by modulating transcription profiles.

Cell migration is essential during animal development. In the Drosophila ovary, the steroid hormone ecdysone coordinates nutrient sensing, growth, and the timing of morphogenesis events including border cell migration. To identify downstream effectors of ecdysone signaling, we profiled gene expression in wild-type follicle cells compared to cells expressing a dominant negative Ecdysone receptor or its coactivator Taiman.

Circuitous Genetic Regulation Governs a Straightforward Cell Migration.

Drosophila border cells undergo a straightforward and stereotypical collective migration during egg development. However, a complex genetic program underlies this process. A variety of approaches, including biochemical, genetic, and imaging strategies have identified many regulatory components, revealing layers of control.

Identification of Novel Regulators of the JAK/STAT Signaling Pathway that Control Border Cell Migration in the Drosophila Ovary.

The Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) signaling pathway is an essential regulator of cell migration both in mammals and fruit flies. Cell migration is required for normal embryonic development and immune response but can also lead to detrimental outcomes, such as tumor metastasis. A cluster of cells termed "border cells" in the Drosophila ovary provides an excellent example of a collective cell migration, in which two different cell types coordinate their movements.

Apontic regulates somatic stem cell numbers in Drosophila testes.

Background: Microenvironments called niches maintain resident stem cell populations by balancing self-renewal with differentiation, but the genetic regulation of this process is unclear. The niche of the Drosophila testis is well-characterized and genetically tractable, making it ideal for investigating the molecular regulation of stem cell biology. The JAK/STAT pathway, activated by signals from a niche component called the hub, maintains both germline and somatic stem cells.

Culturing Drosophila Egg Chambers and Investigating Developmental Processes Through Live Imaging.

Drosophila oogenesis provides many examples of essential processes in development. A myriad of genetic tools combined with recent advances in culturing egg chambers ex vivo has revealed several surprising mechanisms that govern how this tissue develops, and which could not have been determined in fixed tissues. Here we describe a straightforward protocol for dissecting ovaries, culturing egg chambers, and observing egg development in real time by fluorescent microscopy.

Socs36E limits STAT signaling via Cullin2 and a SOCS-box independent mechanism in the Drosophila egg chamber.

The Suppressor of Cytokine Signaling (SOCS) proteins are critical, highly conserved feedback inhibitors of signal transduction cascades. The family of SOCS proteins is divided into two groups: ancestral and vertebrate-specific SOCS proteins. Vertebrate-specific SOCS proteins have been heavily studied as a result of their strong mutant phenotypes.

Tissue landscape alters adjacent cell fates during Drosophila egg development.

Extracellular signalling molecules control many biological processes, but the influence of tissue architecture on the local concentrations of these factors is unclear. Here we examine this issue in the Drosophila egg chamber, where two anterior cells secrete Unpaired (Upd) to activate Signal transducer and activator of transcription (STAT) signalling in the epithelium. High STAT signalling promotes cell motility.

A mathematical model of collective cell migration in a three-dimensional, heterogeneous environment.

Cell migration is essential in animal development, homeostasis, and disease progression, but many questions remain unanswered about how this process is controlled. While many kinds of individual cell movements have been characterized, less effort has been directed towards understanding how clusters of cells migrate collectively through heterogeneous, cellular environments. To explore this, we have focused on the migration of the border cells during Drosophila egg development.

Upright imaging of Drosophila egg chambers.

Drosophila melanogaster oogenesis provides an ideal context for studying varied developmental processes since the ovary is relatively simple in architecture, is well-characterized, and is amenable to genetic analysis. Each egg chamber consists of germ-line cells surrounded by a single epithelial layer of somatic follicle cells. Subsets of follicle cells undergo differentiation during specific stages to become several different cell types.

Phagocytic ability declines with age in adult Drosophila hemocytes.

Most multicellular organisms show a physiological decline in immune function with age. However, little is known about the mechanisms underlying these changes. We examined Drosophila melanogaster, an important model for identifying genes affecting innate immunity and senescence, to explore the role of phagocytosis in age-related immune dysfunction.

Socs36E attenuates STAT signaling to optimize motile cell specification in the Drosophila ovary.

The Janus kinase/Signal transducers and activators of transcription (JAK/STAT) pathway determines cell fates by regulating gene expression. One example is the specification of the motile cells called border cells during Drosophila oogenesis. It has been established that too much or too little STAT activity disrupts follicle cell identity and cell motility, which suggests the signaling must be precisely regulated.

Group choreography: mechanisms orchestrating the collective movement of border cells.

Cell movements are essential for animal development and homeostasis but also contribute to disease. Moving cells typically extend protrusions towards a chemoattractant, adhere to the substrate, contract and detach at the rear. It is less clear how cells that migrate in interconnected groups in vivo coordinate their behaviour and navigate through natural environments.

Age- and diet-specific effects of variation at S6 kinase on life history, metabolic, and immune response traits in Drosophila melanogaster.

Life history theory hypothesizes that genetically based variation in life history traits results from alleles that alter age-specific patterns of energy allocation among the competing demands of reproduction, storage, and maintenance. Despite the important role that alleles with age-specific effects must play in life history evolution, few naturally occurring alleles with age-specific effects on life history traits have been identified. A recent mapping study identified S6 kinase (S6k) as a candidate gene affecting lipid storage in Drosophila.

Interpretation of the UPD/JAK/STAT morphogen gradient in Drosophila follicle cells.

We are using Drosophila follicle cells to study the mechanisms that promote cell motility. Using genetics we identified a gene regulatory network that controls the dynamic pattern of activation of JAK/STAT in anterior follicle cells. Under the influence of a graded signal, Unpaired (UPD), JAK/STAT becomes activated first in a graded fashion.

Hedgehog does not guide migrating Drosophila germ cells.

In many species, the germ cells, precursors of sperm and egg, migrate during embryogenesis. The signals that regulate this migration are thus essential for fertility. In flies, lipid signals have been shown to affect germ cell guidance.

Feedback inhibition of Jak/STAT signaling by apontic is required to limit an invasive cell population.

In both normal development and in a variety of pathological conditions, epithelial cells can acquire migratory and invasive properties. Border cells in the Drosophila ovary provide a genetically tractable model for elucidating the mechanisms controlling such behaviors. Here we report the identification of a mutant, apontic (apt), in which the migratory population expanded and separation from the epithelium was impeded.