ArticleG3 (Bethesda, Md.)2014
Complex cooperative functions of heparan sulfate proteoglycans shape nervous system development in Caenorhabditis elegans.
Article in G3 (Bethesda, Md.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 39 citations in OpenAlex.
- Article
- Heparan Sulfate Proteoglycans: Master Regulators of Cellular Signaling, Tissue Development, and Neural Function.Journal of neuroscience research · 2026Review
- Article
- EFN-4/Ephrin converges with SAX-3/Robo, UNC-6/Netrin, and Heparan Sulfate Proteoglycan signaling to control MAB-5/Hox-dependent posterior Q neuroblast migration inbioRxiv : the preprint server for biology · 2026Article
- Article
- Synthetic Heparan Sulfate Hydrogels Regulate Neurotrophic Factor Signaling and Neuronal Network Activity.ACS applied materials & interfaces · 2022Article
- Emerging chemical and biochemical tools for studying 3-American journal of physiology. Cell physiology · 2022Review
- The Role of Sulfation in Nematode Development and Phenotypic Plasticity.Frontiers in molecular biosciences · 2022Review
- Article
- The CNS/PNS Extracellular Matrix Provides Instructive Guidance Cues to Neural Cells and Neuroregulatory Proteins in Neural Development and Repair.International journal of molecular sciences · 2021Review
- Syndecan receptors: pericellular regulators in development and inflammatory disease.Open biology · 2021Review
- Neural Tissue Homeostasis and Repair Is Regulated via CS and DS Proteoglycan Motifs.Frontiers in cell and developmental biology · 2021Review
- A Brief History of Adherons: The Discovery of Brain Exosomes.International journal of molecular sciences · 2020Review
- Neurite Branching Regulated by Neuronal Cell Surface Molecules inFrontiers in neuroanatomy · 2020Review
- Article
- Anosmin1 Shuttles Fgf to Facilitate Its Diffusion, Increase Its Local Concentration, and Induce Sensory Organs.Developmental cell · 2018Article
- Deciphering functional glycosaminoglycan motifs in development.Current opinion in structural biology · 2018Review
- Synaptogenesis Is Modulated by Heparan Sulfate inGenetics · 2018Article
- Diverse roles for glycosaminoglycans in neural patterning.Developmental dynamics : an official publication of the American Association of Anatomists · 2018Review
- Flexible Roles for Proteoglycan Sulfation and Receptor Signaling.Trends in neurosciences · 2018Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The development of the nervous system is a complex process requiring the integration of numerous molecular cues to form functional circuits. Many cues are regulated by heparan sulfates, a class of linear glycosaminoglycan polysaccharides. These sugars contain distinct modification patterns that regulate protein-protein interactions. Misexpressing the homolog of KAL-1/anosmin-1, a neural cell adhesion molecule mutant in Kallmann syndrome, in Caenorhabditis elegans causes a highly penetrant, heparan sulfate-dependent axonal branching phenotype in AIY interneurons. In an extended forward genetic screen for modifiers of this phenotype, we identified alleles in new as well as previously identified genes involved in HS biosynthesis and modification, namely the xylosyltransferase sqv-6, the HS-6-O-sulfotransferase hst-6, and the HS-3-O-sulfotransferase hst-3.2. Cell-specific rescue experiments showed that different HS biosynthetic and modification enzymes can be provided cell-nonautonomously by different tissues to allow kal-1-dependent branching of AIY. In addition, we show that heparan sulfate proteoglycan core proteins that carry the heparan sulfate chains act genetically in a highly redundant fashion to mediate kal-1-dependent branching in AIY neurons. Specifically, lon-2/glypican and unc-52/perlecan act in parallel genetic pathways and display synergistic interactions with sdn-1/syndecan to mediate kal-1 function. Because all of these heparan sulfate core proteins have been shown to act in different tissues, these studies indicate that KAL-1/anosmin-1 requires heparan sulfate with distinct modification patterns of different cellular origin for function. Our results support a model in which a three-dimensional scaffold of heparan sulfate mediates KAL-1/anosmin-1 and intercellular communication through complex and cooperative interactions. In addition, the genes we have identified could contribute to the etiology of Kallmann syndrome in humans.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.