A high-sugar diet, but not obesity, reduces female fertility in Drosophila melanogaster.

Obesity is linked to reduced fertility in various species, from Drosophila to humans. Considering that obesity is often induced by changes in diet or eating behavior, it remains unclear whether obesity, diet, or both reduce fertility. Here, we show that Drosophila females on a high-sugar diet become rapidly obese and less fertile as a result of increased death of early germline cysts and vitellogenic egg chambers (or follicles).

Chronic exposure to warm temperature causes low sperm abundance and quality in Drosophila melanogaster.

Temperature influences male fertility across organisms; however, how suboptimal temperatures affect adult spermatogenesis remains understudied. In a recent study on Drosophila melanogaster oogenesis, we observed a drastic reduction in the fertility of adult males exposed to warm temperature (29 °C). Here, we show that males become infertile at 29 °C because of low sperm abundance and quality.

Warm and cold temperatures have distinct germline stem cell lineage effects during Drosophila oogenesis.

Despite their medical and economic relevance, it remains largely unknown how suboptimal temperatures affect adult insect reproduction. Here, we report an in-depth analysis of how chronic adult exposure to suboptimal temperatures affects oogenesis using the model insect Drosophila melanogaster. In adult females maintained at 18°C (cold) or 29°C (warm), relative to females at the 25°C control temperature, egg production was reduced through distinct cellular mechanisms.

Hormone receptor 4 is required in muscles and distinct ovarian cell types to regulate specific steps of oogenesis.

The conserved nuclear receptor superfamily has crucial roles in many processes, including reproduction. Nuclear receptors with known roles in oogenesis have been studied mostly in the context of their ovary-intrinsic requirement. Recent studies in , however, have begun to reveal new roles of nuclear receptor signaling in peripheral tissues in controlling reproduction.

RNAi-based screens uncover a potential new role for the orphan neuropeptide receptor Moody in Drosophila female germline stem cell maintenance.

Reproduction is highly sensitive to changes in physiology and the external environment. Neuropeptides are evolutionarily conserved signaling molecules that regulate multiple physiological processes. However, the potential reproductive roles of many neuropeptide signaling pathways remain underexplored.

The Nuclear Receptor Seven Up Regulates Genes Involved in Immunity and Xenobiotic Response in the Adult Female Fat Body.

The physiology of organisms depends on inter-organ communication in response to changes in the environment. Nuclear receptors are broadly expressed transcription factors that respond to circulating molecules to control many biological processes, including immunity, detoxification, and reproduction. Although the tissue-intrinsic roles of nuclear receptors in reproduction have been extensively studied, there is increasing evidence that nuclear receptor signaling in peripheral tissues can also influence oogenesis.

Analysis of Gal4 Expression Patterns in Adult Females.

Precise genetic manipulation of specific cell types or tissues to pinpoint gene function requirement is a critical step in studies aimed at unraveling the intricacies of organismal physiology. researchers heavily rely on the system for tissue-specific manipulations; however, it is often unclear whether the reported Gal4 expression patterns are indeed specific to the tissue of interest such that experimental results are not confounded by secondary sites of Gal4 expression. Here, we surveyed the expression patterns of commonly used drivers in adult female tissues under optimal conditions and found that multiple drivers have unreported secondary sites of expression beyond their published cell type/tissue expression pattern.

Reclaiming Warburg: using developmental biology to gain insight into human metabolic diseases.

Developmental biologists have frequently pushed the frontiers of modern biomedical research. From the discovery and characterization of novel signal transduction pathways to exploring the molecular underpinnings of genetic inheritance, transcription, the cell cycle, cell death and stem cell biology, studies of metazoan development have historically opened new fields of study and consistently revealed previously unforeseen avenues of clinical therapies. From this perspective, it is not surprising that our community is now an integral part of the current renaissance in metabolic research.

Local and Physiological Control of Germline Stem Cell Lineages in .

The long-term survival of any multicellular species depends on the success of its germline in producing high-quality gametes and maximizing survival of the offspring. Studies in have led our growing understanding of how germline stem cell (GSC) lineages maintain their function and adjust their behavior according to varying environmental and/or physiological conditions. This review compares and contrasts the local regulation of GSCs by their specialized microenvironments, or niches; discusses how diet and diet-dependent factors, mating, and microorganisms modulate GSCs and their developing progeny; and briefly describes the tie between physiology and development during the larval phase of the germline cycle.

The nuclear receptor seven up functions in adipocytes and oenocytes to control distinct steps of Drosophila oogenesis.

Reproduction is intimately linked to the physiology of an organism. Nuclear receptors are widely expressed transcription factors that mediate the effects of many circulating molecules on physiology and reproduction. While multiple studies have focused on the roles of nuclear receptors intrinsically in the ovary, it remains largely unknown how the actions of nuclear receptors in peripheral tissues influence oogenesis.

Maintenance of Proper Germline Stem Cell Number Requires Adipocyte Collagen in Adult Females.

Stem cells reside in specialized niches and are regulated by a variety of physiological inputs. Adipocytes influence whole-body physiology and stem cell lineages; however, the molecular mechanisms linking adipocytes to stem cells are poorly understood. Here, we report that collagen IV produced in adipocytes is transported to the ovary to maintain proper germline stem cell (GSC) number in adult females.

Insulin signaling acts in adult adipocytes via GSK-3β and independently of FOXO to control Drosophila female germline stem cell numbers.

Tissue-specific stem cells are tied to the nutritional and physiological environment of adult organisms. Adipocytes have key endocrine and nutrient-sensing roles and have emerged as major players in relaying dietary information to regulate other organs. For example, previous studies in Drosophila melanogaster revealed that amino acid sensing as well as diet-dependent metabolic pathways function in adipocytes to influence the maintenance of female germline stem cells (GSCs).

Steroid Hormones and the Physiological Regulation of Tissue-Resident Stem Cells: Lessons from the Ovary.

Purpose Of Review: Stem cells respond to local paracrine signals; more recently, however, systemic hormones have also emerged as key regulators of stem cells. This review explores the role of steroid hormones in stem cells, using the germline stem cell as a centerpiece for discussion.

Recent Findings: Stem cells sense and respond directly and indirectly to steroid hormones, which regulate diverse sets of target genes via interactions with nuclear hormone receptors.

Adipocyte Metabolic Pathways Regulated by Diet Control the Female Germline Stem Cell Lineage in .

Nutrients affect adult stem cells through complex mechanisms involving multiple organs. Adipocytes are highly sensitive to diet and have key metabolic roles, and obesity increases the risk for many cancers. How diet-regulated adipocyte metabolic pathways influence normal stem cell lineages, however, remains unclear.

Control of Germline Stem Cell Lineages by Diet and Physiology.

Tight coupling of reproduction to environmental factors and physiological status is key to long-term species survival. In particular, highly conserved pathways modulate germline stem cell lineages according to nutrient availability. This chapter focuses on recent in vivo studies in genetic model organisms that shed light on how diet-dependent signals control the proliferation, maintenance, and survival of adult germline stem cells and their progeny.

A visual screen for diet-regulated proteins in the Drosophila ovary using GFP protein trap lines.

The effect of diet on reproduction is well documented in a large number of organisms; however, much remains to be learned about the molecular mechanisms underlying this connection. The Drosophila ovary has a well described, fast and largely reversible response to diet. Ovarian stem cells and their progeny proliferate and grow faster on a yeast-rich diet than on a yeast-free (poor) diet, and death of early germline cysts, degeneration of early vitellogenic follicles and partial block in ovulation further contribute to the ∼60-fold decrease in egg laying observed on a poor diet.

AMP-activated protein kinase has diet-dependent and -independent roles in Drosophila oogenesis.

Multiple aspects of organismal physiology influence the number and activity of stem cells and their progeny, including nutritional status. Previous studies demonstrated that Drosophila germline stem cells (GSCs), follicle stem cells (FSCs), and their progeny sense and respond to diet via complex mechanisms involving many systemic and local signals. AMP-activated protein kinase, or AMPK, is a highly conserved regulator of energy homeostasis known to be activated under low cellular energy conditions; however, its role in the ovarian response to diet has not been investigated.

A Genetic Mosaic Screen Reveals Ecdysone-Responsive Genes Regulating Drosophila Oogenesis.

Multiple aspects of Drosophila oogenesis, including germline stem cell activity, germ cell differentiation, and follicle survival, are regulated by the steroid hormone ecdysone. While the transcriptional targets of ecdysone signaling during development have been studied extensively, targets in the ovary remain largely unknown. Early studies of salivary gland polytene chromosomes led to a model in which ecdysone stimulates a hierarchical transcriptional cascade, wherein a core group of ecdysone-sensitive transcription factors induce tissue-specific responses by activating secondary branches of transcriptional targets.

Genetic Mosaic Analysis of Stem Cell Lineages in the Drosophila Ovary.

Genetic mosaic analyses represent an invaluable approach for the study of stem cell lineages in the Drosophila ovary. The generation of readily identifiable, homozygous mutant cells in the context of wild-type ovarian tissues within intact organisms allows the pinpointing of cellular requirements for gene function, which is particularly important for understanding the physiological control of stem cells and their progeny. Here, we provide a step-by-step guide to the generation and analysis of genetically mosaic ovaries using flippase (FLP)/FLP recognition target (FRT)-mediated recombination in adult Drosophila melanogaster, with a focus on the processes of oogenesis that are controlled by diet-dependent factors.

Gut healing: haemocytes aid via Sax and Tkv jazzes it down.

Control of stem cell activity is essential for accurate regeneration. Pathogen- or chemical-induced intestinal damage is now shown to recruit haemocytes expressing bone morphogenetic protein signals that stimulate proliferation of intestinal stem cells and subsequently induce their quiescence, in conjunction with muscle-derived bone morphogenetic proteins. A temporal switch in expression of Type I receptors enables this two-phase response.

Ecdysone response gene E78 controls ovarian germline stem cell niche formation and follicle survival in Drosophila.

Nuclear hormone receptors have emerged as important regulators of mammalian and Drosophila adult physiology, affecting such seemingly diverse processes as adipogenesis, carbohydrate metabolism, circadian rhythm, stem cell function, and gamete production. Although nuclear hormone receptors Ecdysone Receptor (EcR) and Ultraspiracle (Usp) have multiple known roles in Drosophila development and regulate key processes during oogenesis, the adult function of the majority of nuclear hormone receptors remains largely undescribed. Ecdysone-induced protein 78C (E78), a nuclear hormone receptor closely related to Drosophila E75 and to mammalian Rev-Erb and Peroxisome Proliferator Activated Receptors, was originally identified as an early ecdysone target; however, it has remained unclear whether E78 significantly contributes to adult physiology or reproductive function.

Insulin-independent role of adiponectin receptor signaling in Drosophila germline stem cell maintenance.

Adipocytes have key endocrine roles, mediated in large part by secreted protein hormones termed adipokines. The adipokine adiponectin is well known for its role in sensitizing peripheral tissues to insulin, and several lines of evidence suggest that adiponectin might also modulate stem cells/precursors. It remains unclear, however, how adiponectin signaling controls stem cells and whether this role is secondary to its insulin-sensitizing effects or distinct.

Adipocyte amino acid sensing controls adult germline stem cell number via the amino acid response pathway and independently of Target of Rapamycin signaling in Drosophila.

How adipocytes contribute to the physiological control of stem cells is a critical question towards understanding the link between obesity and multiple diseases, including cancers. Previous studies have revealed that adult stem cells are influenced by whole-body physiology through multiple diet-dependent factors. For example, nutrient-dependent pathways acting within the Drosophila ovary control the number and proliferation of germline stem cells (GSCs).

Control of adult stem cells in vivo by a dynamic physiological environment: diet-dependent systemic factors in Drosophila and beyond.

Adult stem cells are inextricably linked to whole-body physiology and nutrient availability through complex systemic signaling networks. A full understanding of how stem cells sense and respond to dietary fluctuations will require identifying key systemic mediators, as well as elucidating how they are regulated and integrated with local and intrinsic factors across multiple tissues. Studies focused on the Drosophila germline have generated valuable insights into how stem cells are controlled by diet-dependent pathways, and increasing evidence suggests that diverse adult stem cell populations respond to nutrients through similar mechanisms.

Cyclin E controls Drosophila female germline stem cell maintenance independently of its role in proliferation by modulating responsiveness to niche signals.

Stem cells must proliferate while maintaining 'stemness'; however, much remains to be learned about how factors that control the division of stem cells influence their identity. Multiple stem cell types display cell cycles with short G1 phases, thought to minimize susceptibility to differentiation factors. Drosophila female germline stem cells (GSCs) have short G1 and long G2 phases, and diet-dependent systemic factors often modulate G2.