An Epidermal MicroRNA Regulates Neuronal Migration Through Control of the Cellular Glycosylation State

An appropriate balance in glycosylation of proteoglycans is crucial for their ability to regulate animal development. Here, we report that the Caenorhabditis elegans microRNA mir-79, an ortholog of mammalian miR-9, controls sugar-chain homeostasis by targeting two proteins in the proteoglycan biosyn...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2013-09, Vol.341 (6152), p.1404-1408
Main Authors: Pedersen, Mikael Egebjerg, Snieckute, Goda, Kagias, Konstantinos, Nehammer, Camilla, Multhaupt, Hinke A. B., Couchman, John R., Pocock, Roger
Format: Article
Language:English
Subjects:
Animal migration behavior
Animals
Axons
Biological and medical sciences
Biosynthesis
Caenorhabditis elegans
Caenorhabditis elegans - metabolism
Caenorhabditis elegans - physiology
Caenorhabditis elegans Proteins - biosynthesis
Caenorhabditis elegans Proteins - genetics
Caenorhabditis elegans Proteins - metabolism
Cell adhesion & migration
Cell Movement
Cellular biology
Epidermis - metabolism
Fundamental and applied biological sciences. Psychology
Glycosylation
Glycosyltransferases - metabolism
Glypicans - biosynthesis
Glypicans - genetics
Heparan Sulfate Proteoglycans - biosynthesis
Heparan Sulfate Proteoglycans - genetics
Hypodermis
Journalism
MicroRNA
MicroRNAs - genetics
MicroRNAs - physiology
Migration
Monosaccharide Transport Proteins - metabolism
Neurons
Neurons - physiology
Nucleobase, Nucleoside, Nucleotide, and Nucleic Acid Transport Proteins - metabolism
Phenotypes
Proteoglycans
Ribonucleic acid
RNA
Sulfates
Vertebrates: nervous system and sense organs
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Summary:An appropriate balance in glycosylation of proteoglycans is crucial for their ability to regulate animal development. Here, we report that the Caenorhabditis elegans microRNA mir-79, an ortholog of mammalian miR-9, controls sugar-chain homeostasis by targeting two proteins in the proteoglycan biosynthetic pathway: a chondroitin synthase (SQV-5; squashed vulva-5) and a uridine 5'-diphosphate—sugar transporter (SQV-7). Loss of mir-79 causes neurodevelopmental defects through SQV-5 and SQV-7 dysregulation in the epidermis. This results in a partial shutdown of heparan sulfate biosynthesis that impinges on a LON-2/glypican pathway and disrupts neuronal migration. Our results identify a regulatory axis controlled by a conserved microRNA that maintains proteoglycan homeostasis in cells.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1242528