Biology subjects

Zhang, M. G.

Publications and source records attributed to Zhang, M. G..

4 recordsLinked to original sources

bioRxiv2024

Neuronal activity regulating the dauer entry decision in Caenorhabditis elegans

The model nematode Caenorhabditis elegans can choose between two alternative developmental trajectories. Larvae can either become reproductive adults or, under conditions of crowding or low food availability, enter a long-term, stress-resistant diapause known as the dauer stage. Previous studies showed that chemical signals from a secreted larval pheromone promote the dauer trajectory, and that their influence can be antagonised by increased availability of microbial food. The decision is known to be under neuronal control, involving both sensory and interneurons. To make an accurate decision, larvae must collect and compare complex patterns of environmental input over several hours of early larval development. The full composition of this circuit and the algorithm for decision-making are unknown. Here, we used cell-specific chemical silencing to systematically perturb several sensory and interneurons to further elucidate circuit composition. Our results suggest a role for gas-sensing neurons in regulating dauer entry. In addition, we quantitatively characterized the neuronal responses to food and pheromone inputs by measuring calcium traces from ASI and AIA neurons. We found that calcium in ASI increases linearly in response to food, and similarly decreases in response to pheromone, revealing a cellular site of antagonism between these key chemical inputs. Notably, the ASI response persists well beyond removal of the food stimulus, thus encoding a memory of recent food exposure. In contrast, AIA reports instantaneous food availability, and is unaffected by pheromone. We discuss how these findings may inform our understanding of this long-term decision-making process.

neuroscience↗

bioRxiv2024

Sensory integration of food availability and population density during the diapause exit decision involves insulin-like signaling in Caenorhabditis elegans

Decisions made over long time scales, such as life cycle decisions, require coordinated interplay between sensory perception and sustained gene expression. The Caenorhabditis elegans dauer (or diapause) exit developmental decision requires sensory integration of population density and food availability to induce an all-or-nothing organismal-wide response, but the mechanism by which this occurs remains unknown. Here, we demonstrate how the ASJ chemosensory neurons, known to be critical for dauer exit, perform sensory integration at both the levels of gene expression and calcium activity. In response to favorable conditions, dauers rapidly produce and secrete the dauer exit-promoting insulin-like peptide INS-6. Expression of ins-6 in the ASJ neurons integrate population density and food level and can reflect decision commitment since dauers committed to exiting have higher ins-6 expression levels than those of non-committed dauers. Calcium imaging in dauers reveals that the ASJ neurons are activated by food, and this activity is suppressed by pheromone, indicating that sensory integration also occurs at the level of calcium transients. We find that ins-6 expression in the ASJ neurons depends on neuronal activity in the ASJs, cGMP signaling, a CaM-kinase pathway, and the pheromone components ascr#8 and ascr#2. We propose a model in which decision commitment to exit the dauer state involves an autoregulatory feedback loop in the ASJ neurons that promotes high INS-6 production and secretion. These results collectively demonstrate how insulin-like peptide signaling helps animals compute long-term decisions by bridging sensory perception to decision execution. Summary/Significance StatementAnimals must respond appropriately to multiple sensory stimuli to make informed decisions. It remains unclear how the nervous system is able to integrate different sensory cues and propagate that information towards making decisions over longer timescales. We use the nematode Caenorhabditis elegans to investigate how sensory integration occurs during the decision to exit diapause, a stress-resistant developmentally arrested state triggered by multiple sensory inputs including food availability and population density. We show how expression of an insulin-like peptide critical to dauer exit reflects the sensory integration process and decision commitment, and we dissect the regulation of this insulin-like peptides expression. Our study explicitly analyzes the relationship between neuronal activity and neuropeptide expression during a complex decision with diverse sensory inputs.

neuroscience↗

bioRxiv2023

Fluorescence dynamics of lysosomal-related organelle flashing in the intestinal cells of Caenorhabditis elegans

The lysosome-related organelles ("gut granules") in the intestinal cells of many nematodes, including Caenorhabditis elegans, play an important role in metabolic and signaling processes, but they have not been fully characterized. We report here a previously undescribed phenomenon in which the autofluorescence of these granules displays a "flash" phenomenon in which fluorescence decreases are preceded by sharp increases in fluorescence intensity that expand into the surrounding area when the granules are stimulated with blue light. Autofluorescent granules are present in the intestinal cells of all six nematode species examined, with differences in morphology and distribution pattern. Five species exhibit the flash phenomenon: Panagrellus redivivus (Clade IV), Steinernema hermaphroditum (Clade IV), C. elegans (Clade V), Oscheius tipulae (Clade V), and Pristionchus pacificus (Clade V). The reaction of the granules to blue light stimulation greatly differs among different developmental stages and may also be dependent on physiological conditions. In addition, even within the same animal, the sensitivity of individual granules differs, with some of the variation associated with other characteristics of the granules, such as their overall location within the intestine. We hypothesize that the differences in response to blue light indicate the existence of different sub-populations of gut granules in nematode intestines, and the visually spectacular dynamic fluorescence phenomenon we describe might provide a handle on their eventual characterization.

cell biology↗

bioRxiv2021

Entry to and exit from diapause arrest in Caenorhabditis elegans are both regulated by a steroid hormone pathway

Diapause arrest in animals such as Caenorhabditis elegans is tightly regulated so that animals make appropriate developmental decisions amidst environmental challenges. Fully understanding diapause requires mechanistic insight of both entry and exit from the arrested state. While a steroid hormone pathway regulates the entry decision into Caenorhabditis elegans dauer diapause, its role in the exit decision is less clear. A complication to understanding steroid hormonal regulation of dauer has been the peculiar fact that steroid hormone mutants such as daf-9 form partial dauers under normal growth conditions. Here, we corroborate previous findings that daf-9 mutants remain capable of forming full dauers under unfavorable growth conditions, and we establish that the daf-9 partial dauer state is likely a partially exited dauer that has initiated but cannot complete the dauer exit decision. We show that the steroid hormone pathway is both necessary for and promotes complete dauer exit, and that the spatiotemporal dynamics of steroid hormone regulation during dauer exit resembles that of dauer entry. Overall, dauer entry and dauer exit are distinct developmental decisions that are both controlled by steroid hormone signaling. Summary StatementIn animals such as Caenorhabditis elegans, a steroid hormone pathway controls both the entry and exit decisions into and out of the developmentally arrested dauer state in response to environmental signaling.

developmental biology↗