Biology subjects

Christensen, C. F.

Publications and source records attributed to Christensen, C. F..

3 recordsLinked to original sources

bioRxiv2025

Monoamine-induced diacylglycerol signaling rapidly accumulates Unc13 in nanoclusters for fast presynaptic potentiation

Neuromodulators control mood, arousal, and behavior by inducing synaptic plasticity via G-protein coupled receptors. Long-term potentiation of presynaptic neurotransmitter release requires structural changes, but how fast potentiation is achieved within minutes remains enigmatic. Using the Drosophila melanogaster neuromuscular junction, we show that on the timescale of one minute, octopamine, the invertebrate analog of nor-epinephrine, rapidly potentiates evoked neurotransmitter release by a G protein coupled pathway involving presynaptic OAMB receptors and phospholipase C. No changes of presynaptic calcium influx were seen, but confocal signals of the release factor Unc13A and the scaffolding protein Bruchpilot increased within one minute of octopamine treatment. On the same timescale, live, single-molecule imaging of endogenously tagged Unc13 revealed its instantly reduced motility and its increased concentration in synaptic nanoclusters with potentiation. Presynaptic knockdown of Unc13A fully blocked fast potentiation and removal of its N-terminal localization sequence delocalized the protein fragment to the cytosol, but it was rapidly recruited to the plasma membrane by DAG analog phorbol esters and octopamine, pointing to a role in C-terminal domains. Point mutation of endogenous Unc13 disrupting diacylglycerol-binding to its C1 domain blocked plasticity-induced nanoscopic enrichment and synaptic potentiation. The mutation increased basal neurotransmission but reduced Unc13 levels, revealing a gain of function and potential homeostatic compensation. The mutation also blocked phorbol ester-induced potentiation, decreased the calcium-sensitivity of neurotransmission and caused short-term synaptic depression. At the organismal level, the mutation reduced locomotion and survival while enhancing reproduction. Thus, the Unc13 C1 domain mediates acute subsynaptic compaction of Unc13 under monoamine-induced potentiation and influences short-term plasticity, locomotion, reproduction, and survival.

neuroscience↗

bioRxiv2024

Pvf1-PvR-mediated crosstalk between the trachea and the gut guides intestinal stem cell migration to promote gut regeneration.

In adult tissues, stem cells (SCs) reside in specialized niches, where they are maintained in a quiescent state until activated by injury. Once activated, they migrate towards injured sites, where they proliferate and differentiate to replenish lost or damaged cells. Although effective tissue repair relies critically on the ability of SCs to reach and populate damaged sites, mechanisms guiding SCs towards these sites are not well understood. This is largely due to the technical challenges involved in monitoring SC dynamics in real time in vivo. Here, we devised an experimental framework that allows for real-time tracking of the spatiotemporal dynamics of intestinal SCs (ISCs) during the early phases of gut regeneration. Our data show that ISC migration is rapidly induced following injury and precedes ISC divisions and differentiation. We identify the Drosophila PDGF-VEGF-related receptor, Pvr, as a critical regulator of the migratory response to epithelial damage. ISC-specific Pvr depletion strongly suppresses ISC migration towards affected sites as well as the regenerative response. We further show that the Pvr ligand, PDGF-VEGF-related factor 1 (Pvf1), is produced by the trachea/vasculature in response to intestinal damage and acts as a guidance signal to direct ISC migration towards affected areas. Our work highlights a critical role of gut-trachea/vasculature crosstalk in guiding ISC migration during regeneration. As neovascularization of injured sites is a key feature of tissue repair in both flies and mammals, these findings could be relevant to regenerative processes in a wide range of adult tissues.

physiology↗

bioRxiv2023

Drosophila activins adapt gut size to food intake and promote regenerative growth

Rapidly renewable tissues adapt different strategies to cope with environmental insults. While tissue repair is associated with increased ISC proliferation and accelerated tissue turnover rates, reduced calorie intake triggers a homeostasis-breaking process causing adaptive resizing of the gut. Here we show that activins are key drivers of both adaptive and regenerative growth. Activin-{beta} (Act-{beta}) is produced by progenitor cells in response to intestinal infections and stimulates ISC proliferation and turnover rates to promote tissue repair. Dawdle (Daw), a divergent Drosophila activin, signals through its receptor, BaboC, in progenitor cells to promote their maturation into enterocytes (ECs). Daw is dynamically regulated during starvation-refeeding cycles, where it couples nutrient intake with progenitor maturation and adaptive resizing of the gut. Our results highlight an activin-dependent mechanism coupling nutrient intake with progenitor-to-EC maturation to promote adaptive resizing of the gut and further establish activins as key regulators of adult tissue plasticity.

physiology↗