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

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Science  20 Sep 2013:
Vol. 341, Issue 6152, pp. 1404-1408
DOI: 10.1126/science.1242528

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Extracellular Regulation

During Caenorhabditis elegans development, the hermaphrodite-specific neurons (HSNs) migrate and then extend axons toward their functional targets. Posttranslational modification of heparan sulfate proteoglycans are important for HSN development, and so Pedersen et al. (p. 1404) tested the effect of disrupting or reducing chondroitin and heparan sulfate synthesis during C. elegans development. The results suggest that proteoglycan biosynthesis is tightly regulated by a microRNA pathway to shape the cell surface glycosylation architecture required to direct neuronal migration.

Abstract

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.

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