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Biology subjects

Nahid, M. A.

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

3 recordsLinked to original sources

The Drosophila Secretome

Secreted proteins are synthesized within the cell and actively transported outside, where they contribute to development, physiology, immunity, and cellcell communication. In Drosophila melanogaster, many secreted signaling pathways are evolutionarily conserved, making this species a powerful model for studying human development, cancer, neurobiology, and immune regulation. To assemble the Drosophila secretome, we systematically analyzed all fly protein sequences with computational tools, integrating FlyBase, UniProt and Gene Ontology annotations, and incorporating large-scale proteomics datasets. We identified 4,831 genes encoding putative secreted proteins, assigned confidence scores based on the type and strength of supporting evidence, and generated an online resource (www.flyrnai.org/apps/fly_secretome/) for exploring these data. Comparison with the human secretome shows that 54% of Drosophila secretome genes are conserved in the human genome and of these, 83% are annotated as secreted in human. In addition, comparison with Drosophila single-cell transcriptomic data revealed that secreted proteins are more tissue-specific than other genes. Finally, we demonstrate the utility of this resource by analyzing changes in expression of genes encoding putative secreted proteins during aging based on snRNA-seq datasets from the Aging Fly Cell Atlas.

genetics↗

Maternal lipids prime quiescent neural stem cells to reactivate in response to dietary nutrients

Stem cell quiescence--a state of mitotic and metabolic dormancy--is essential for tissue homeostasis and for coordinating growth with nutrient availability. Switching between quiescence and proliferation is controlled through stem cell intrinsic and extrinsic cues, with diet being key as diet provides macro-and micro-nutrients needed for synthesizing new membrane, protein, and nucleic acids. Yet, it remains unclear what nutrients control the stem cell switch and whether nutrient sources other than diet are required. Here, we report that lipids deposited maternally in the embryo regulate reactivation of Drosophila neural stem cells (neuroblasts) from quiescence. This maternal nutrient source is in addition to the known dietary amino acids required during larval feeding1. Females fed reduced lipid diets or carrying mutations in genes essential for lipid deposition and metabolism produce larvae with fewer stored lipids in neural tissues. Reduced neural lipid stores result in delayed glial growth and neuroblast reactivation due to the inability of neuroblasts to activate PI3-kinase signaling in response to diet-induced expression of insulin-like peptides. Thus, neuroblasts rely on two nutrient sources, maternal and dietary, raising the possibility that quiescent stem cells in general access and utilize stored and acquired nutrients coordinately to switch between stem cell states.

developmental biology↗

Delta-dependent Notch activation closes the early neuroblast temporal program to promote lineage progression and neurogenesis termination in Drosophila

Neuroblasts in Drosophila divide asymmetrically, sequentially expressing a series of intrinsic factors to generate a diversity of neuron types. These intrinsic factors known as temporal factors dictate timing of neuroblast transitions in response to steroid hormone signaling and specify early versus late temporal fates in neuroblast neuron progeny. After completing their temporal programs, neuroblasts differentiate or die, finalizing both neuron number and type within each neuroblast lineage. From a screen aimed at identifying genes required to terminate neuroblast divisions, we identified Notch and Notch pathway components. When Notch is knocked down, neuroblasts maintain early temporal factor expression longer, delay late temporal factor expression, and continue dividing into adulthood. We find that Delta, expressed in cortex glia, neuroblasts, and after division, their GMC progeny, regulates neuroblast Notch activity. We also find that Delta in neuroblasts is expressed high early, low late, and is controlled by the intrinsic temporal program: early factor Imp promotes Delta, late factors Syp/E93 reduce Delta. Thus, in addition to systemic steroid hormone cues, forward lineage progression is controlled by local cell-cell signaling between neuroblasts and their cortex glia/GMC neighbors: Delta transactivates Notch in neuroblasts bringing the early temporal program and early temporal factor expression to a close.

developmental biology↗