Biology subjects

Siegrist, S.

Publications and source records attributed to Siegrist, S..

3 recordsLinked to original sources

bioRxiv2026

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↗

bioRxiv2024

Notch controls early temporal factor expression to control timing of Mushroom body neuroblast apoptosis

The neurogenic period, where neural stem cells (NSCs) proliferate to produce molecularly distinct progeny in the developing brain, is a critical time of growth in many organisms. Proper brain development is crucial for survival and requires strict regulation of NSC divisions along a set developmental timeline. In Drosophila NSCs known as neuroblasts (NBs), cell intrinsic programs integrate with extrinsic cues to control periods of rapid growth through temporal patterning genes. Without regulation, NSCs can under proliferate leading to diseases like microcephaly and autism spectrum disorders, or over proliferate leading to macrocephaly and tumors. We know programs to control timing of proliferation and elimination of NSCs exist, but many elements of temporal cassettes are still unclear. What genes may be upstream to regulate known temporal programs to control when certain progeny are produced have not been fully identified, leaving a gap in our understanding. To address these questions, we carried out a large-scale RNAi screen aimed at identifying genes required for NSC elimination. We identified Notch and its ligand, Delta. When Notch pathway activity is reduced in NSCs, we found premature elimination of an important subset of neuroblasts called the mushroom body neuroblasts (MBNBs). These MBNBs produce the neurons responsible for formation of the evolutionarily conserved structure called the mushroom body (MB), which is involved in olfactory based learning and memory. MBNBs with reduced Notch pathway activity also experienced defects in MB structure. Furthermore, we determined that temporal patterning is disrupted primarily through loss of early temporal factor expression. In this work, we find that cell signaling pathways that involve the receptor Notch and its ligand. Delta function to regulate NB proliferation in Drosophila melanogaster by regulating early temporal factor expression.

developmental biology↗

bioRxiv2019

Membrane compartmentalization of mycobacterial peptidoglycan synthesis

Many antibiotics target the assembly of cell wall peptidoglycan, an essential, heteropolymeric mesh that encases most bacteria. Different species have characteristic subcellular sites of peptidoglycan synthesis that they must carefully maintain for surface integrity and, ultimately, viability. In rod-shaped bacteria, cell wall elongation is spatially precise yet relies on a limited pool of lipid-linked precursors that generate and are attracted to membrane disorder. By tracking enzymes, substrates and products of peptidoglycan biosynthesis in Mycobacterium smegmatis, we show that precursors are made in plasma membrane domains that are laterally and biochemically distinct from sites of cell wall assembly. Membrane partitioning is required for robust, orderly peptidoglycan synthesis, indicating that these domains help template peptidoglycan synthesis. The cell wall-organizing protein DivIVA and the cell wall itself are essential for domain homeostasis. Thus, the peptidoglycan polymer feeds back on its membrane template to maintain an environment conducive to directional synthesis. We further show that our findings are applicable to rod-shaped bacteria that are phylogenetically distant from M. smegmatis, demonstrating that horizontal compartmentalization of precursors is a general feature of bacillary cell wall biogenesis.Competing Interest StatementThe authors have declared no competing interest.View Full Text

microbiology↗