Biology subjects

Mast, J.

Publications and source records attributed to Mast, J..

4 recordsLinked to original sources

bioRxiv2025

Investigation of the molecular-genetic basis for courtship differences between Drosophila melanogaster, Drosophila simulans and their hybrids

Understanding the mechanisms driving behavioral evolution enhances our knowledge of speciation and how behavioral potentials are genetically encoded. Male courtship behaviors, which evolve rapidly, are critical for pre-mating isolation. To investigate the genetic basis of species-specific courtship, we generated hybrid males by crossing two Drosophila melanogaster strains with D. simulans Lhr males. This design allowed us to assess how genetic background and female species identity influence male courtship behavior. In both single-pair and mate-choice assays, hybrid males displayed behavioral plasticity, adjusting their courtship strategies based on the female species. The maternal D. melanogaster strain significantly shaped hybrid behavioral repertoires. To identify the neural correlates, we examined fruitless (fru)-expressing neurons in hybrids. Their projection patterns resembled those in D. melanogaster, indicating conserved circuit architecture. Using CUT&Tag, we identified FruM target genes in both species, revealing conserved core and species-specific FruM targets. Focusing on chemosensory receptors with D. melanogaster-specific FruM binding, we conducted a genetic screen in D. melanogaster, silencing neurons co-expressing fru P1 and specific receptor genes. Courtship preference assays identified three additional olfactory receptor neuron subtypes that modulate species-specific behavior. Using trans-Tango, we mapped second-order projection neurons of these subtypes, revealing their targets in higher-order brain centers. This study uncovers new molecular and neural mechanisms underlying the specification and evolution of courtship behavior, highlighting how genetic and sensory inputs shape species-specific behavioral outcomes. Article SummaryWe examined how genes and circuits shape courtship behaviors in Drosophila melanogaster and Drosophila simulans. Hybrid males adjust their behavior based on the species of female, suggesting flexible courtship. We focused on the fruitless gene, which controls male courtship. fru neurons in hybrids closely resembled those in Drosophila melanogaster. We identified both shared and species-specific FruM target genes. A genetic screen of odorant receptor neurons revealed populations that help males distinguish females. Neuroanatomical mapping shows the odor information is relayed to different higher order brain regions. The results uncover molecular and neural circuit mechanisms underlying species differences in behaviors.

neuroscience↗

bioRxiv2023

Characterization of erythroferrone oligomerization and its impact on BMP antagonism

Hepcidin, a peptide hormone that negatively regulates iron metabolism, is expressed by bone morphogenetic protein (BMP) signaling. Erythroferrone (ERFE) is an extracellular protein that binds and inhibits BMP ligands, thus positively regulating iron import by indirectly suppressing hepcidin. This allows for rapid erythrocyte regeneration after blood loss. ERFE belongs to the C1Q/TNF related protein (CTRP) family and is suggested to adopt multiple oligomeric forms: a trimer, a hexamer, and a high molecular weight species. The molecular basis for how ERFE binds BMP ligands and how the different oligomeric states impact BMP inhibition are poorly understood. In this study, we demonstrated that ERFE activity is dependent on the presence of stable dimeric or trimeric ERFE, and that larger species are dispensable for BMP inhibition. Additionally, we used an in-silico approach to identify a helix, termed the ligand binding domain (LBD), that was predicted to bind BMPs and occlude the type I receptor pocket. We provide evidence that the LBD is crucial for activity through luciferase assays and surface plasmon resonance (SPR) analysis. Our findings provide new insight into how ERFE oligomerization impacts BMP inhibition, while identifying critical molecular features of ERFE essential for binding BMP ligands.

molecular biology↗

bioRxiv2020

Structural and functional impact of the H5 hemagglutinin expression into a NDV vector vaccine backbone

Recombinant Newcastle disease viruses (rNDV) have been used as bivalent vectors for vaccination against multiple economically important avian pathogens. NDV-vectored vaccines expressing the immunogenic H5 hemagglutinin (rNDV-H5) are considered attractive candidates to protect poultry from both highly pathogenic avian influenza (HPAI) and Newcastle disease (ND). However, the impact of the insertion of a recombinant protein, such as H5, on the biological characteristics of the parental NDV strain has been little investigated to date. The present study compared a rNDV-H5 vaccine and its parental NDV LaSota strain in terms of their structural and functional characteristics, as well as their recognition by the innate immune sensors. Structural analysis of the rNDV-H5 demonstrated a decreased number of fusion (F) and a higher number of hemagglutinin-neuraminidase (HN) glycoproteins compared to NDV LaSota. These structural differences were accompanied by increased hemagglutinating and neuraminidase activities of rNDV-H5. During in vitro rNDV-H5 infection, increased mRNA expression of TLR3, TLR7, MDA5, and LGP2 was observed, suggesting that the recombinant virus is recognized differently by sensors of innate immunity when compared with the parental NDV LaSota. Given the growing interest in using NDV as a vector against human and animal diseases, these data highlight the importance to thoroughly understand the recombinant vaccines structural organization, functional characteristics, and the immune responses elicited.

microbiology↗

bioRxiv2018

Defects in the neuroendocrine axis cause global development delay in aDrosophila model of NGLY1 Deficiency

N-glycanase 1 (NGLY1) Deficiency is a rare monogenic multi-system disorder first described in 2014. NGLY1 is evolutionarily conserved in model organisms, including the Drosophila melanogaster NGLY1 homolog, Pngl. Here we conducted a natural history study and chemical-modifier screen on a new fly model of NGLY1 Deficiency engineered with a nonsense mutation in Pngl at codon 420, resulting in truncation of the C-terminal carbohydrate-binding PAW domain. Homozygous mutant animals exhibit global development delay, pupal lethality and small body size as adults. We developed a 96-well-plate, image-based, quantitative assay of Drosophila larval size for use in a screen of the 2,650-member Microsource Spectrum compound library of FDA approved drugs, bioactive tool compounds, and natural products. We found that the cholesterol-derived ecdysteroid molting hormone 20-hydroxyecdysone (20E) rescued the global developmental delay in mutant homozygotes. Targeted expression of a human NGLY1 transgene to tissues involved in ecdysteroidogenesis, e.g., prothoracic gland, also rescues global developmental delay in mutant homozygotes. Finally, the proteasome inhibitor bortezomib is a potent enhancer of global developmental delay in our fly model, evidence of a defective proteasome \"bounce-back\" response that is also observed in nematode and cellular models of NGLY1 Deficiency. Together, these results demonstrate the therapeutic relevance of a new fly model of NGLY1 Deficiency for drug discovery, biomarker discovery, pharmacodynamics studies, and gene modifier screens.

genetics↗