Biology subjects

Corcoran, S.

Publications and source records attributed to Corcoran, S..

5 recordsLinked to original sources

bioRxiv2025

Exosome secretion is required for sonic hedgehog dispersal and signal gradient formation in the embryonic limb mesenchyme

Carrier-assisted diffusion and cytoneme transport have been postulated to disperse Hedgehog across diverse embryonic tissues, yet their relative contributions to patterning mesenchymal tissues remains poorly understood. Here, we combine novel signaling assays with quantitative microscopy to establish exosome secretion as a predominant and adaptable mechanism for Sonic Hedgehog (Shh) dispersal. Introducing a novel synchronous release system to visualize Shh trafficking in embryonic tissues, we demonstrate that Shh traffics through the exosome biogenesis pathway in the limb bud mesenchyme. Shh-bound exosomes diffuse through extracellular space, and can also bind and travel along cytonemes, providing a potential mechanism for directed and/or long-range transport. Using a synthetic patterning assay, we show that exosome secretion is essential to establish short-range Shh gradients in vitro. We propose that exosome-based Shh secretion, combined with different modes of extracellular transport, provides a tunable mechanism to sculpt Shh gradients on different length and time scales, across different embryonic tissues. HIGHLIGHTSO_LIA novel synchronous release system reveals trafficking dynamics in embryonic cells C_LIO_LISonic hedgehog is packaged and secreted on exosomes for extracellular dispersal C_LIO_LIExosome secretion is required to establish short-range Hedgehog gradients C_LIO_LIDiffusion and cytoneme transport provide tunable exosome dispersal strategies C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/692671v1_ufig1.gif" ALT="Figure 1"> View larger version (89K): org.highwire.dtl.DTLVardef@76b266org.highwire.dtl.DTLVardef@ba5b4borg.highwire.dtl.DTLVardef@bf9d67org.highwire.dtl.DTLVardef@1f6d699_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2024

Temporal cohort number, neural composition, and connectivity vary along the Drosophila larval body axis

Neural stem cells are inherently flexible, producing different lineages of neurons in different contexts; yet in vivo, development must be highly regulated because aberrant stem cell development leads to microcephalies, tumors, and neurodevelopmental disorders. However, the full complement of in vivo flexibility in neural stem cell development remains poorly understood. Within the Drosophila CNS, 30 types of neural stem cells or neuroblasts repeat in each segment with segment-specific differences in development. We studied NB3-3 neuroblast in each of the 14 segments where it is present. In different segments, NB3-3 produces different types of neurons in different numbers but always produces Even-skipped Lateral (EL) neurons. Prior work showed that in abdominal segments, ELs comprise two types of temporal cohorts. Temporal cohorts are small sets of neurons within a lineage that are born within a tight time window. In the abdomen, EL neurons in the early-born temporal cohort all receive mechanosensory input, whereas EL neurons in the late-born temporal cohort all receive proprioceptive input. Herein, we find that NB3-3 generates an early-born EL temporal cohort in all segments. In specific regions, NB3-3 neuroblasts produce additional types of temporal cohorts, including but not limited to the late-born EL temporal cohort. We show that variations in NB3-3 division pattern determine the number and type of temporal cohorts. Later in development, the number of neurons within a temporal cohort is refined by a variety of post-mitotic mechanisms: regulation of molecular identity markers, cell death, and differentiation status, acting in complex combinations in different segments. Post-mitotic refinement of neuron numbers occurs most often for neurons of the early-born EL temporal cohort. Further, neurons of the early-born EL temporal cohort are incorporated into different circuits, depending on segment. Together, our results show how a single neural stem cell type can flexibly generate segment-specific lineages and contribute to various circuits. We offer the following framework for understanding how a given type of neural stem cell generates diverse temporal cohorts: a stem cell type invariably generates one type of temporal cohort, regardless of location or pattern of division. For neurons in this invariant temporal cohort, post-mitotic mechanisms introduce diversity in number. The stem cell, on a segment-by-segment basis, can also produce additional types of temporal cohorts simply by altering its division pattern. This framework is valuable for motor circuit development, the development of sexual dimorphisms, nervous system evolution, and in vitro stem cell applications.

neuroscience↗

bioRxiv2020

Dscam1 promotes blood cell survival in Drosophila melanogaster through a dual role in blood cells and neurons

Down Syndrome Cell Adhesion Molecule 1 (Dscam1) is a receptor-like cell adhesion molecule that is conserved across the animal kingdom, but its roles in hematopoiesis remain unknown. Dscam1 related genes in vertebrates and invertebrates are key regulators of neuron morphogenesis and neuronal tiling. In Drosophila, Dscam1 in addition has roles in blood cells (hemocytes) in innate immunity and phagocytosis of pathogens. Given the anatomical and functional role of peripheral sensory neurons as microenvironments for resident hematopoietic sites in the Drosophila larva, we sought to investigate the role of Dscam1 in this context. Interestingly, we find that Dscam1 fills the role of a previously anticipated factor in neuron-hemocyte communication that supports trophic survival: tissue specific silencing of Dscam1 by in vivo RNAi in sensory neurons leads to neuron reduction, which in turn results in reduced hemocyte numbers due to apoptosis. Dscam1 silencing in hemocytes also results in a reduction of hemocytes and increased apoptosis. This cell-autonomous effect of Dscam1 silencing can be mimicked by RNAi silencing of dreadlocks (dock), suggesting that intracellular Dscam1 signaling relies on the adapter protein Dock in this system. Our findings reveal a dual role for Dscam1 in Drosophila hematopoiesis, by promoting survival of the sensory neuron microenvironments that in turn support hemocyte survival, and by promoting survival of hemocytes cell-autonomously. It will be interesting to explore possible functions of vertebrate Dscam1 related genes such as DSCAML1 in blood cells and their trophic survival.

developmental biology↗

bioRxiv2020

Regulation of blood cell transdifferentiation by oxygen sensing neurons in Drosophila

Transdifferentiation generates specialized cell types independent of stem or progenitor cells. Despite the unique process, it remains poorly understood how transdifferentiation is regulated in vivo. Here we reveal a mechanism of environmental control of blood cell transdifferentiation in a Drosophila model of hematopoiesis. Functional lineage tracing provides evidence for transdifferentiation from macrophage-like plasmatocytes to crystal cells that execute melanization. Interestingly, this transdifferentiation is promoted by neuronal activity of a specific subset of sensory neurons, in the caudal sensory cones of the larva. Crystal cells develop from plasmatocyte clusters surrounding the sensory cones, triggered by environmental conditions: oxygen sensing, and the atypical guanylyl cyclase Gyc88E specifically expressed in the sensory cone neurons, drive plasmatocyte-to-crystal cell transdifferentiation. Our findings reveal an unexpected functional and molecular link of environment-monitoring sensory neurons that govern blood cell transdifferentiation in vivo, suggesting similar principles in vertebrate systems where environmental sensors and blood cell populations coincide. HighlightsO_LIFunctional lineage tracing reveals in vivo transdifferentiation in a Drosophila model of hematopoiesis C_LIO_LIActive sensory neurons of the caudal sensory cones promote blood cell transdifferentiation in the Drosophila larva C_LIO_LIEnvironmental oxygen sensing and atypical guanylyl cyclase activity in sensory cone neurons drive blood cell transdifferentiation C_LI

developmental biology↗

bioRxiv2019

Blood cells of adult Drosophila do not expand, but control survival after bacterial infection by induction of Drosocin around their reservoir at the respiratory epithelia

Drosophila melanogaster has been an excellent model for innate immunity, but the role and regulation of adult blood cells and organismal immunity have remained incompletely understood. Here we address these questions in a comprehensive investigation of the blood cell system in adult Drosophila. As a central finding, we reveal the largest reservoir of blood cells (hemocytes) at the respiratory epithelia (tracheal air sacs) and fat body of the thorax and head. We show that most hemocytes of adult Drosophila are phagocytic macrophages (plasmatocytes), derived by more than 60% from the embryonic lineage that parallels vertebrate tissue macrophages. Surprisingly, in contrast to hemocytes at the larval stage, we find no capacity of the adult blood cell system to expand. Instead, we demonstrate its central role in relaying an innate immune response to tissues surrounding the blood cell reservoir: Hemocytes, through Imd signaling and the Jak/Stat pathway ligand Upd3, act as sentinels of bacterial infection that induce expression of the antimicrobial peptide gene Drosocin in the respiratory epithelia and colocalizing domains of the fat body. We demonstrate that endogenous Drosocin expression in these tissues promotes animal survival after bacterial infection. Our work identifies the first molecular step in a new relay of organismal immunity, establishing adult Drosophila as model to dissect mechanisms of inter-organ immunity.

immunology↗