A muscle-epidermis-glia signaling axis sustains synaptic specificity during allometric growth in Caenorhabditis elegans

Synaptic positions underlie precise circuit connectivity. Synaptic positions can be established during embryogenesis and sustained during growth. The mechanisms that sustain synaptic specificity during allometric growth are largely unknown. We performed forward genetic screens in C. elegans for regulators of this process and identified mig-17, a conserved ADAMTS metalloprotease. Proteomic mass spectrometry, cell biological and genetic studies demonstrate that MIG-17 is secreted from cells like muscles to regulate basement membrane proteins. In the nematode brain, the basement membrane does not directly contact synapses. Instead, muscle-derived basement membrane coats one side of the glia, while glia contact synapses on their other side. MIG-17 modifies the muscle-derived basement membrane to modulate epidermal-glial crosstalk and sustain glia location and morphology during growth. Glia position in turn sustains the synaptic pattern established during embryogenesis. Our findings uncover a muscle-epidermis-glia signaling axis that sustains synaptic specificity during the organism’s allometric growth.

• Publication year

  2020

• Venue

  eLife

• Publication date

  2020-04-07

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.7554/eLife.55890PMID 32255430PMCID 7164957
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Cell surface molecule, Klingon, mediates the refinement of synaptic specificity in the Drosophila visual system

  2019cited by this paper
• Glial regulation of synapse maturation and stabilization in the developing nervous system.

  2019cited by this paper
• The Astrocyte-Neuron Interface: An Overview on Molecular and Cellular Dynamics Controlling Formation and Maintenance of the Tripartite Synapse.

  2019cited by this paper
• Collagen XIII and Other ECM Components in the Assembly and Disease of the Neuromuscular Junction

  2019influential reference
• Synaptogenic pathways.

  2019cited by this paper
• Demystifying the extracellular matrix and its proteolytic remodeling in the brain: structural and functional insights

  2019cited by this paper
• Basement membrane and blood–brain barrier

  2018cited by this paper
• Genetic Suppression of Basement Membrane Defects in Caenorhabditis elegans by Gain of Function in Extracellular Matrix and Cell-Matrix Attachment Genes

  2018cited by this paper
• Fundamental Molecules and Mechanisms for Forming and Maintaining Neuromuscular Synapses

  2018cited by this paper
• Maintenance mechanisms of circuit-integrated axons.

  2018cited by this paper
• Enzyme and Chemical Assisted N-Terminal Blocked Peptides Analysis, ENCHANT, as a Selective Proteomics Approach Complementary to Conventional Shotgun Approach.

  2018cited by this paper
• Molecular Mechanisms of Synaptic Specificity: Spotlight on Hippocampal and Cerebellar Synapse Organizers

  2018cited by this paper
• Collagen VI is required for the structural and functional integrity of the neuromuscular junction

  2018influential reference
• Allometric scaling of brain regions to intra‐cranial volume: An epidemiological MRI study

  2017cited by this paper
• The extracellular metalloprotease AdamTS-A anchors neural lineages in place within and preserves the architecture of the central nervous system

  2017cited by this paper
• Neural Cell Adhesion Molecules of the Immunoglobulin Superfamily Regulate Synapse Formation, Maintenance, and Function.

  2017cited by this paper
• The role of laminins in the organization and function of neuromuscular junctions.

  2017cited by this paper
• Clarinet (CLA-1), a novel active zone protein required for synaptic vesicle clustering and release

  2017cited by this paper
• Synthesis and deposition of basement membrane proteins by primary brain capillary endothelial cells in a murine model of the blood–brain barrier

  2017cited by this paper
• A report of three families with FBN1-related acromelic dysplasias and review of literature for genotype-phenotype correlation in geleophysic dysplasia.

  2017cited by this paper
• Cell Biology of Astrocyte-Synapse Interactions.

  2017cited by this paper
• Mechanisms of input and output synaptic specificity: finding partners, building synapses, and fine-tuning communication.

  2017cited by this paper
• Organ Length Control by an ADAMTS Extracellular Protease in Caenorhabditis elegans

  2016cited by this paper
• A Two-Immunoglobulin-Domain Transmembrane Protein Mediates an Epidermal-Neuronal Interaction to Maintain Synapse Density.

  2016cited by this paper
• SPARC Promotes Cell Invasion In Vivo by Decreasing Type IV Collagen Levels in the Basement Membrane

  2016cited by this paper
• The extracellular protease stl functions to inhibit migration of v'ch1 sensory neuron during Drosophila embryogenesis.

  2015cited by this paper
• Control of the basement membrane and cell migration by ADAMTS proteinases: Lessons from C. elegans genetics.

  2015cited by this paper
• Streamlined Genome Engineering with a Self-Excising Drug Selection Cassette

  2015cited by this paper
• Two classes of matrix metalloproteinases reciprocally regulate synaptogenesis

  2015influential reference
• Glial development and function in the nervous system of Caenorhabditis elegans.

  2015cited by this paper
• Astrocyte-encoded positional cues maintain sensorimotor circuit integrity

  2014cited by this paper
• Regulation of Synaptic Extracellular Matrix Composition Is Critical for Proper Synapse Morphology

  2014cited by this paper
• Neural ECM and synaptogenesis.

  2014cited by this paper
• The conserved LIM domain-containing focal adhesion protein ZYX-1 regulates synapse maintenance in Caenorhabditis elegans

  2014cited by this paper
• Perlecan Antagonizes Collagen IV and ADAMTS9/GON-1 in Restricting the Growth of Presynaptic Boutons

  2014influential reference
• Synapse location during growth depends on glia location.

  2013cited by this paper
• Engineering the Caenorhabditis elegans Genome Using Cas9-Triggered Homologous Recombination

  2013cited by this paper
• CloudMap: A Cloud-Based Pipeline for Analysis of Mutant Genome Sequences

  2012cited by this paper
• Tissue Architecture in the Caenorhabditis elegans Gonad Depends on Interactions Among Fibulin-1, Type IV Collagen and the ADAMTS Extracellular Protease

  2012influential reference
• Selective Decline of Synaptic Protein Levels in the Frontal Cortex of Female Mice Deficient in the Extracellular Metalloproteinase ADAMTS1

  2012cited by this paper
• The Caenorhabditis elegans epidermis as a model skin. I: development, patterning, and growth

  2012cited by this paper
• Regional Astrocyte Allocation Regulates CNS Synaptogenesis and Repair

  2012cited by this paper
• The Caenorhabditis elegans epidermis as a model skin. II: differentiation and physiological roles

  2012cited by this paper
• Basement Membrane Sliding and Targeted Adhesion Remodels Tissue Boundaries During Uterine-vulval Attachment in C. elegans

  2011cited by this paper
• Role of extracellular matrix proteins and their receptors in the development of the vertebrate neuromuscular junction

  2011cited by this paper
• Connecting vascular and nervous system development: angiogenesis and the blood-brain barrier.

  2010cited by this paper
• Molecular mechanisms of synaptic specificity.

  2010cited by this paper
• Mechanisms of synapse and dendrite maintenance and their disruption in psychiatric and neurodegenerative disorders.

  2010cited by this paper
• A robust method to estimate the intracranial volume across MRI field strengths (1.5T and 3T)

  2010cited by this paper
• Regulation of synaptic connectivity by glia

  2010cited by this paper
• Looking beyond development: maintaining nervous system architecture.

  2009cited by this paper
• Synapse formation in developing neural circuits.

  2009cited by this paper
• Universal sample preparation method for proteome analysis

  2009cited by this paper
• Multiplex peptide stable isotope dimethyl labeling for quantitative proteomics

  2009cited by this paper
• Many paths to synaptic specificity.

  2009cited by this paper
• Astrocytes and the regulation of cerebral blood flow.

  2009cited by this paper
• MIG-17/ADAMTS controls cell migration by recruiting nidogen to the basement membrane in C. elegans

  2008cited by this paper
• Stage‐specific activation of MIG‐17/ADAMTS controls cell migration in Caenorhabditis elegans

  2008cited by this paper
• Bergmann Glia and the Recognition Molecule CHL1 Organize GABAergic Axons and Direct Innervation of Purkinje Cell Dendrites

  2008influential reference
• Glia Promote Local Synaptogenesis Through UNC-6 (Netrin) Signaling in C. elegans

  2007cited by this paper
• The Neurovascular Unit and the Key Role of Astrocytes in the Regulation of Cerebral Blood Flow

  2006cited by this paper
• WormAtas Hermaphrodite Handbook - Introduction

  2006cited by this paper
• Metalloproteinase ADAMTS-1 but not ADAMTS-5 is manifold overexpressed in neurodegenerative disorders as Down syndrome, Alzheimer's and Pick's disease.

  2005cited by this paper
• Epidermal morphogenesis.

  2005cited by this paper
• A fibulin-1 homolog interacts with an ADAM protease that controls cell migration in C. elegans.

  2004influential reference
• Basal lamina and the organization of neuromuscular synapses

  2003cited by this paper
• The immunoglobulin superfamily protein SYG-1 determines the location of specific synapses in C. elegans.

  2003cited by this paper
• The Basement Membrane Components Nidogen and Type XVIII Collagen Regulate Organization of Neuromuscular Junctions inCaenorhabditis elegans

  2003cited by this paper
• A novel mode of ecdysozoan growth in Caenorhabditis elegans

  2002cited by this paper
• Control of synapse number by glia.

  2001influential reference
• A metalloprotease disintegrin that controls cell migration in Caenorhabditis elegans.

  2000cited by this paper
• Visualization of synaptic specializations in live C. elegans with synaptic vesicle protein-GFP fusions.

  1999cited by this paper
• A new gene, encoding an anion transporter, is mutated in sialic acid storage diseases

  1999cited by this paper
• Mutations affecting symmetrical migration of distal tip cells in Caenorhabditis elegans.

  1999cited by this paper
• Type IV Collagen Is Detectable in Most, but Not All, Basement Membranes of Caenorhabditis elegans and Assembles on Tissues That Do Not Express It

  1997cited by this paper
• Characterization of α1(IV) Collagen Mutations in Caenorhabditis elegans and the Effects of α1 and α2(IV) Mutations on Type IV Collagen Distribution

  1997influential reference
• Caenorhabditis elegans rab-3 Mutant Synapses Exhibit Impaired Function and Are Partially Depleted of Vesicles

  1997cited by this paper
• Genes critical for muscle development and function in Caenorhabditis elegans identified through lethal mutations

  1994cited by this paper
• Genetic identification, sequence, and alternative splicing of the Caenorhabditis elegans alpha 2(IV) collagen gene

  1993cited by this paper
• Embryonic lethality caused by mutations in basement membrane collagen of C. elegans

  1991influential reference
• Efficient gene transfer in C.elegans: extrachromosomal maintenance and integration of transforming sequences.

  1991cited by this paper
• [Genetics of Caenorhabditis elegans].

  1989influential reference
• The structure of the nervous system of the nematode Caenorhabditis elegans.

  1986influential reference
• Immunological identification of the genes encoding the four myosin heavy chain isoforms of Caenorhabditis elegans.

  1986cited by this paper
• Differential localization of two myosins within nematode thick filaments.

  1983cited by this paper
• The genetics of Caenorhabditis elegans.

  1974influential reference
• Terminology of Relative Growth

  1936cited by this paper
• Constant Differential Growth-Ratios and their Significance

  1924cited by this paper
• Constant Differential Growth-ratios and their Significance

  year unknowncited by this paper

• Remodeling of extracellular matrix collagen IV by MIG-6/papilin regulates neuronal architecture

  2025cites this paper
• Live visualization of extracellular matrix dynamics during development and regeneration in zebrafish

  2025cites this paper
• Exploring Basement Membrane Dynamics through Cross-Scale Imaging, Manipulation, and Molecular Mapping.

  2025cites this paper
• Interplay between MIG-6/papilin and TGF-β signaling promotes extracellular matrix remodeling and modulates the maintenance of neuronal architecture

  2025cites this paper
• Unveiling the Hidden World of Octopus Glia

  2025cites this paper
• A collagen IV fluorophore knock-in toolkit reveals trimer diversity in C. elegans basement membranes.

  2025cites this paper
• O-GlcNAc transferase promotes synaptic assembly independent of catalytic activity in C. elegans

  2025cites this paper
• Glia Development and Function in the Nematode Caenorhabditis elegans.

  2024cites this paper
• Cellular and Molecular Mechanisms Underlying Synaptic Subcellular Specificity

  2024cites this paper
• Age-progressive interplay of HSP-proteostasis, ECM-cell junctions and biomechanics ensures C. elegans astroglial architecture

  2024cites this paper
• OGT‐1 regulates synaptic assembly through the insulin signaling pathway

  2023cites this paper
• Cell‐based allometry: an approach for evaluation of complexity in morphogenesis

  2023cites this paper
• An interplay of HSP-proteostasis, biomechanics and ECM-cell junctions ensures C. elegans astroglial architecture

  2023cites this paper
• Establishment and Maintenance of Neural Circuit Architecture

  2021cites this paper
• Temperature regulates synaptic subcellular specificity mediated by inhibitory glutamate signaling

  2021cites this paper
• Loss of the Extracellular Matrix Protein DIG-1 Causes Glial Fragmentation, Dendrite Breakage, and Dendrite Extension Defects

  2021cites this paper
• Glia-derived temporal signals orchestrate neurogenesis in the Drosophila mushroom body

  2021cites this paper
• A neurite-zippering mechanism, mediated by layer-specific expression of IgCAMs, regulates synaptic laminar specificity in the C. elegans nerve ring neuropil

  2020cites this paper