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      Regulation of Drosophila hematopoietic sites by Activin-β from active sensory neurons

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          Abstract

          An outstanding question in animal development, tissue homeostasis and disease is how cell populations adapt to sensory inputs. During Drosophila larval development, hematopoietic sites are in direct contact with sensory neuron clusters of the peripheral nervous system (PNS), and blood cells (hemocytes) require the PNS for their survival and recruitment to these microenvironments, known as Hematopoietic Pockets. Here we report that Activin-β, a TGF-β family ligand, is expressed by sensory neurons of the PNS and regulates the proliferation and adhesion of hemocytes. These hemocyte responses depend on PNS activity, as shown by agonist treatment and transient silencing of sensory neurons. Activin-β has a key role in this regulation, which is apparent from reporter expression and mutant analyses. This mechanism of local sensory neurons controlling blood cell adaptation invites evolutionary parallels with vertebrate hematopoietic progenitors and the independent myeloid system of tissue macrophages, whose regulation by local microenvironments remain undefined.

          Abstract

          Hematopoietic sites in the Drosophila larva require the local peripheral nervous system for blood cells (hemocytes) to survive and proliferate, but how this is mediated is unclear. Here, the authors identify Activin-β from sensory neurons as signalling to hemocytes, affecting proliferation and adhesion.

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          Most cited references50

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          Alveolar macrophages: plasticity in a tissue-specific context.

          Alveolar macrophages exist in a unique microenvironment and, despite historical evidence showing that they are in close contact with the respiratory epithelium, have until recently been investigated in isolation. The microenvironment of the airway lumen has a considerable influence on many aspects of alveolar macrophage phenotype, function and turnover. As the lungs adapt to environmental challenges, so too do alveolar macrophages adapt to accommodate the ever-changing needs of the tissue. In this Review, we discuss the unique characteristics of alveolar macrophages, the mechanisms that drive their adaptation and the direct and indirect influences of epithelial cells on them. We also highlight how airway luminal macrophages function as sentinels of a healthy state and how they do not respond in a pro-inflammatory manner to antigens that do not disrupt lung structure. The unique tissue location and function of alveolar macrophages distinguish them from other macrophage populations and suggest that it is important to classify macrophages according to the site that they occupy.
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            GFP Reconstitution Across Synaptic Partners (GRASP) defines cell contacts and synapses in living nervous systems.

            The identification of synaptic partners is challenging in dense nerve bundles, where many processes occupy regions beneath the resolution of conventional light microscopy. To address this difficulty, we have developed GRASP, a system to label membrane contacts and synapses between two cells in living animals. Two complementary fragments of GFP are expressed on different cells, tethered to extracellular domains of transmembrane carrier proteins. When the complementary GFP fragments are fused to ubiquitous transmembrane proteins, GFP fluorescence appears uniformly along membrane contacts between the two cells. When one or both GFP fragments are fused to synaptic transmembrane proteins, GFP fluorescence is tightly localized to synapses. GRASP marks known synaptic contacts in C. elegans, correctly identifies changes in mutants with altered synaptic specificity, and can uncover new information about synaptic locations as confirmed by electron microscopy. GRASP may prove particularly useful for defining connectivity in complex nervous systems.
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              Non-Smad Signaling Pathways of the TGF-β Family.

              Ying Zhang (2017)
              Transforming growth factor β (TGF-β) and structurally related factors use several intracellular signaling pathways in addition to Smad signaling to regulate a wide array of cellular functions. These non-Smad signaling pathways are activated directly by ligand-occupied receptors to reinforce, attenuate, or otherwise modulate downstream cellular responses. This review summarizes the current knowledge of the mechanisms by which non-Smad signaling pathways are directly activated in response to ligand binding, how activation of these pathways impinges on Smads and non-Smad targets, and how final cellular responses are affected in response to these noncanonical signaling modes.
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                Author and article information

                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group
                2041-1723
                27 July 2017
                2017
                : 8
                : 15990
                Affiliations
                [1 ]Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, and Department of Cell and Tissue Biology, University of California San Francisco , San Francisco, California 94143, USA
                [2 ]Department of Genetics, Cell Biology and Development, University of Minnesota , Minneapolis, Minnesota 55455, USA
                [3 ]Cardiovascular Research Institute, and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco , San Francisco, California 94143, USA
                Author notes
                [*]

                Present address: Institute of Science and Technology (IST) Austria, 3400 Klosterneuburg, Austria

                Article
                ncomms15990
                10.1038/ncomms15990
                5537569
                28748922
                b2770118-ebf0-42bc-bbaf-0eb1e26b5126
                Copyright © 2017, The Author(s)

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 13 May 2015
                : 23 May 2017
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