An epidermal microRNA regulates neuronal migration through control of the cellular glycosylation state

Mikael Egebjerg Pedersen; Goda Snieckute; Konstantinos Kagias; Camilla Nehammer; Hinke A B Multhaupt; John R Couchman; Roger Pocock

doi:10.1126/science.1242528

An epidermal microRNA regulates neuronal migration through control of the cellular glycosylation state

Mikael Egebjerg Pedersen, Goda Snieckute, Konstantinos Kagias, Camilla Nehammer, Hinke A B Multhaupt, John R Couchman, Roger Pocock

Nutritional Immunology

59 Citations (Scopus)

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.

Original language	English
Journal	Science
Volume	341
Issue number	6152
Pages (from-to)	1404-8
Number of pages	5
ISSN	0036-8075
DOIs	https://doi.org/10.1126/science.1242528
Publication status	Published - 20 Sept 2013

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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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T1 - An epidermal microRNA regulates neuronal migration through control of the cellular glycosylation state

AU - Pedersen, Mikael Egebjerg

AU - Snieckute, Goda

AU - Kagias, Konstantinos

AU - Nehammer, Camilla

AU - Multhaupt, Hinke A B

AU - Couchman, John R

AU - Pocock, Roger

PY - 2013/9/20

Y1 - 2013/9/20

N2 - 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.

AB - 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.

U2 - 10.1126/science.1242528

DO - 10.1126/science.1242528

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An epidermal microRNA regulates neuronal migration through control of the cellular glycosylation state

Abstract

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