Biology subjects

Welte, M. A.

Publications and source records attributed to Welte, M. A..

7 recordsLinked to original sources

bioRxiv2026

Monitoring Fatty Acid Trafficking during Drosophila oogenesis Reveals a Role for the Triglyceride Synthase DGAT1 in Protecting Mitochondrial Integrity

Successful oogenesis requires the precise coordination of nutrient uptake, storage, and utilization to meet the high metabolic demands of egg production. In mammals, fatty acid (FA) metabolism has emerged as a key driver of oocyte maturation; however, the mechanisms by which follicles regulate FA trafficking and utilization remain poorly understood across all systems. To address these issues, we leverage the genetic tractability of Drosophila melanogaster oogenesis. We found that nurse cell mitochondria are metabolically active and catabolize FA in a stage-dependent manner, with fatty acid oxidation (FAO) peaking during mid-oogenesis. By exposing explanted follicles to fluorescently labeled FAs, we monitored FA trafficking and found massive enrichment in lipid droplets. Mutants for the triglyceride lipase ATGL exhibited a reduction in both mitochondrial membrane potential and FAO, suggesting that mitochondria utilize FA from triglycerides stored in LDs. To determine the significance of this transient FA storage in LDs, we prevented the formation of nurse cell LDs with mutations in the triglyceride synthase DGAT1. The DGAT1 mutant follicles display excess accumulation of FAs in mitochondria, mitochondrial stress, and developmental arrest. We find that this mitochondrial dysfunction and follicle arrest are consequences of FA toxicity to mitochondria: limiting FA influx into follicles or FA import into mitochondria alleviates these defects. Our findings demonstrate that LD-derived FAs are actively mobilized to fuel the energy demands of oogenesis while LDs buffer against lipotoxicity, revealing a critical balance between FA storage and oxidation. These findings highlight LDs as central hubs regulating energy homeostasis and developmental progression in the follicle. Author SummaryOogenesis places extraordinary metabolic demands on the follicle, yet the energy source for follicle development is not well understood. In fruit flies, follicles take in large amounts of lipids from the hemolymph, the insect blood, and accumulate massive fat stores in the form of lipid droplets. Whether these stores are reserved for the embryo or already power oogenesis was unclear. Using mutants and fluorescent probes for metabolic activity, we found that some fatty acids are released from the lipid droplets and power energy production in mitochondria; this energy source is important for successful oogenesis. We then fed flies fluorescently labeled fatty acids and determined how these fatty acids travel when lipid droplet formation can occur versus when it is abolished. In the former case, fatty acids accumulate in lipid droplets; in the latter, they flood into mitochondria, causing mitochondrial dysfunction, reduced ATP levels, and follicle death. We can correct all these defects by limiting lipid influx specifically into mitochondria. Our findings reveal an important role for lipid droplets during oogenesis. They act as a metabolic buffer, supplying sufficient amounts of fatty acids to mitochondria for energy production while shielding the mitochondria from toxic lipid levels.

developmental biology↗

bioRxiv2026

H2A.Z levels control the timing of major events at the maternal-zygotic transition

Across animals, early embryonic events are temporally tightly coordinated but the underlying mechanisms remain incompletely understood. In Drosophila, both global and nuclear levels of the histone variant H2Av rise progressively during the maternal-zygotic transition (MZT), but whether this increase is functionally important is unknown. We find that increased H2Av dosage expedites specific MZT events: the transition from nuclear cycle (NC) 13 to 14 occurs prematurely as does the turnover of thousands of maternal transcripts; in addition, a subset of genes is precociously expressed in the zygote. Reduced H2Av dosage has reciprocal effects. Comparable transcriptional shifts are observed in zebrafish embryos overexpressing the H2Av ortholog H2A.Z, suggesting H2Av/H2A.Z dosage as a conserved timer of early development. We also examined mutants with impaired H2Av sequestration on lipid droplets which exhibit increased nuclear H2Av levels but reduced cytoplasmic levels. Unexpectedly, nuclear H2Av abundance influences the timing of NC 13 but is not the main driver of transcriptome remodeling. In summary, we find that H2Av/H2A.Z levels are critical timers of early embryogenesis and that H2Av can act in part via a non-nuclear mechanism. Author summaryIn animals, the earliest stages of embryogenesis are initially driven by proteins and RNAs that the mother provides via the egg; later development is controlled by the embryos own genes. The switch from maternal to zygotic control is called the maternal-zygotic transition (MZT). This conserved process involves degradation of maternal mRNAs, activation of zygotic genes, cell cycle lengthening, and morphological remodeling. All these events require precise control, but how they are coordinated remains incompletely understood. Here we show that the levels of a specific histone, H2A.Z, provide a timer for the MZT. In Drosophila, H2A.Z levels - both in the embryo overall and in nuclei - increase during the MZT. When we ectopically increased H2A.Z levels, specific MZT events occurred prematurely. Reducing H2A.Z levels had the opposite effect. Using mutant flies in which H2A.Z levels are ectopically increased in the nucleus but reduced in the embryo as a whole, we uncovered both nuclear and non-nuclear roles for H2A.Z in the establishment of developmental timing. Moreover, we observed similar outcomes in genetically manipulated zebrafish embryos. Our results are consistent with an ancient mechanism in which H2A.Z abundance functions as a timer of early embryogenesis.

developmental biology↗

bioRxiv2026

Drosophila Heat Shock Factor (HSF) Regulates Developmental Growth by Maintaining the Basal Expression of HSP83/HSP90

The heat shock transcription factor HSF1 is best known as a master regulator of the proteotoxic stress response, yet its functions in animal development remain incompletely defined. In Drosophila melanogaster, heat shock factor (HSF) is essential for viability, but the mechanisms by which it promotes development are unclear. Here, we show that Hsf null larvae arrest at the early 2nd instar stage and exhibit a significant reduction in basal levels of the chaperone HSP83/HSP90. Tissue-specific knockdown of Hsf revealed widespread and organ-specific requirements, including defects in endoreplication and cell growth in larval prothoracic and salivary glands, adult wing defects following larval imaginal disc perturbation, follicle degeneration in the ovary, and melanotic tumor upon hemocyte depletion. In these tissues, loss of HSF typically leads to reduced HSP83 levels, and restoration of HSP83 expression partially or fully rescues these defects. These findings identify HSP83 as a critical downstream effector of HSF and demonstrate that HSF promotes development largely by maintaining basal chaperone expression. Together, our results establish HSF as a key regulator of developmental progression and highlight a central role for proteostasis in supporting tissue growth under non-stress conditions.

developmental biology↗

bioRxiv2025

The lipid droplet protein Jabba promotes actin remodeling downstream of prostaglandin signaling during Drosophila oogenesis

Growing evidence supports that lipid droplets (LDs) are critical for producing high-quality oocytes. However, the functions of LDs during oocyte development remain largely unknown. Using Drosophila oogenesis as a model, we previously discovered the LD-associated Adipose Triglyceride Lipase (ATGL) promotes actin remodeling necessary for oocyte development by providing the substrate for producing lipid signals termed prostaglandins (PGs). Here we find that Jabba, a LD-associated protein best known for its role in anchoring other proteins to LDs, also promotes PG-dependent actin remodeling. Overexpression of Jabba results in thickened cortical actin and excessive actin bundles, whereas loss of Jabba results in cortical actin breakdown and severely defective actin bundle formation. We find that Jabba regulates actin remodeling independently of ATGL but in conjunction with PG signaling. These data support that there are two PG signaling pathways that promote actin remodeling: one PG pathway that is dependent on ATGL and the other requires Jabba. Overexpression of Jabba rescues the actin defects when PG signaling is lost. Together these data lead to the model that PGs produced independently of ATGL positively regulate Jabba to promote actin remodeling necessary for follicle morphogenesis and the production of a fertilization competent oocyte. Significance statementO_LIAcross organisms, lipid droplets accumulate during oocyte development and are implicated in fertility. The functions of lipid droplets during oogenesis are poorly understood. C_LIO_LIThe authors use the genetic tools and well-characterized process of Drosophila oogenesis to reveal that Jabba, a lipid droplet anchoring protein, is a new downstream effector of prostaglandin signaling and promotes actin remodeling necessary for producing a fertilization competent oocyte. C_LIO_LIThe results extend prior studies connecting lipid droplet proteins, prostaglandins, and actin remodeling, providing insight into how these critical conserved factors contribute to high-quality oocytes. C_LI

cell biology↗

bioRxiv2022

Drosophila embryos spatially sort their nutrient stores to facilitate their utilization

Animal embryos are provisioned by their mothers with a diverse nutrient supply critical for development. In Drosophila, the three most abundant nutrients (triglycerides, proteins, and glycogen) are sequestered in distinct storage structures, lipid droplets (LDs), yolk vesicles (YVs) and glycogen granules (GGs). Using transmission electron microscopy as well as live and fixed-sample fluorescence imaging, we find that all three storage structures are dispersed throughout the egg but are then spatially allocated to distinct tissues by gastrulation: LDs largely to the peripheral epithelium, YVs and GGs to the central yolk cell. To confound the embryos ability to sort its nutrients, we employ mutants in Jabba and Mauve to generate LD:GG or LD:YV compound structures. In these mutants, LDs are missorted to the yolk cell and their turnover is delayed. Our observations demonstrate dramatic spatial nutrient sorting in early embryos and provide the first evidence for its functional importance.

developmental biology↗

bioRxiv2021

Lipid droplets regulate actin remodeling via prostaglandin signaling during Drosophila oogenesis

A key factor controlling oocyte quality and fertility is lipids. Even though lipid droplets (LDs) are crucial regulators of lipid metabolism, their roles in fertility are poorly understood. During Drosophila oogenesis, LD accumulation in nurse cells coincides with dynamic actin remodeling necessary for late-stage follicle morphogenesis and fertility. Loss of the LD-associated Adipose Triglyceride Lipase (ATGL) disrupts both actin bundle formation and cortical actin integrity, an unusual phenotype also seen when Pxt, the enzyme responsible for prostaglandin (PG) synthesis, is missing. Dominant genetic interactions and PG treatment of follicles in vitro reveal that ATGL and Pxt act in the same pathway to regulate actin remodeling, with ATGL upstream of Pxt. Further, lipidomic analysis detects arachidonic acid (AA) containing triglycerides in ovaries. Because AA is the substrate for Pxt, we propose that ATGL releases AA from LDs to drive PG synthesis necessary for follicle development. We also find that exogenous AA is toxic to follicles in vitro, and LDs modulate this toxicity. This leads to the model that LDs both sequester AA to limit toxicity, and release AA via ATGL to drive PG production. We speculate that the same pathways are conserved across organisms to regulate oocyte development and promote fertility.

cell biology↗

bioRxiv2020

Sequestration to lipid droplets promotes histone availability by preventing turnover of excess histones

Because dearth and overabundance of histones result in cellular defects, histone synthesis and demand are typically tightly coupled. In Drosophila embryos, histones H2B/H2A/H2Av accumulate on lipid droplets (LDs), cytoplasmic fat storage organelles. Without this binding, maternally provided H2B/H2A/H2Av are absent; however, the molecular basis of how LDs ensure histone storage is unclear. Using quantitative imaging, we uncover when during oogenesis these histones accumulate, and which step of accumulation is LD-dependent. LDs originate in nurse cells and are transported to the oocyte. Although H2Av accumulates on LDs in nurse cells, the majority of the final H2Av pool is synthesized in oocytes. LDs promote intercellular transport of the histone-anchor Jabba and thus its presence in the ooplasm. Jabba prevents ooplasmic H2Av from degradation, safeguarding the H2Av stockpile. Our findings provide insight into the mechanism for establishing histone stores during Drosophila oogenesis and shed light on the function of LDs as protein-sequestration sites.

cell biology↗