SDN-1/Syndecan Acts in Parallel to the Transmembrane Molecule MIG-13 to Promote Anterior Neuroblast Migration

Sundararajan, Lakshmi; Norris, Megan L; Lundquist, Erik A.

doi:10.1534/g3.115.018770

Cited by 20 publications

(29 citation statements)

References 49 publications

(134 reference statements)

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“…A number of HSPGs have been characterized in C . elegans using mutations that affect specific core proteins , such as mutations in sdn-1 /syndecan, lon-2 /glypican, cle-1 /collagen type XVIII, unc-52 /perlecan, gpn-1/ glypican, and agr-1/ agrin [6–26]. These studies have uncovered precise roles of individual HSPGs in morphogenesis and nervous system development.…”

Section: Introductionmentioning

confidence: 99%

Functional Requirements for Heparan Sulfate Biosynthesis in Morphogenesis and Nervous System Development in C. elegans

et al. 2017

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The regulation of cell migration is essential to animal development and physiology. Heparan sulfate proteoglycans shape the interactions of morphogens and guidance cues with their respective receptors to elicit appropriate cellular responses. Heparan sulfate proteoglycans consist of a protein core with attached heparan sulfate glycosaminoglycan chains, which are synthesized by glycosyltransferases of the exostosin (EXT) family. Abnormal HS chain synthesis results in pleiotropic consequences, including abnormal development and tumor formation. In humans, mutations in either of the exostosin genes EXT1 and EXT2 lead to osteosarcomas or multiple exostoses. Complete loss of any of the exostosin glycosyltransferases in mouse, fish, flies and worms leads to drastic morphogenetic defects and embryonic lethality. Here we identify and study previously unavailable viable hypomorphic mutations in the two C. elegans exostosin glycosyltransferases genes, rib-1 and rib-2. These partial loss-of-function mutations lead to a severe reduction of HS levels and result in profound but specific developmental defects, including abnormal cell and axonal migrations. We find that the expression pattern of the HS copolymerase is dynamic during embryonic and larval morphogenesis, and is sustained throughout life in specific cell types, consistent with HSPGs playing both developmental and post-developmental roles. Cell-type specific expression of the HS copolymerase shows that HS elongation is required in both the migrating neuron and neighboring cells to coordinate migration guidance. Our findings provide insights into general principles underlying HSPG function in development.

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Section: Introductionmentioning

confidence: 99%

Functional Requirements for Heparan Sulfate Biosynthesis in Morphogenesis and Nervous System Development in C. elegans

et al. 2017

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“…Although numerous molecules have been identified that act in the Q cells to promote migration, such as the transmembrane receptors UNC-40/DCC, PTP-3/ LAR, and MIG-13 (Sundararajan and Lundquist 2012;Wang et al 2013;Sundararajan et al 2015), fewer have been identified that act outside the Q cells to control their migration. Of the nonautonomous genes that have been implicated in Q-descendant migration, most are secreted molecules such as Wnts (Hunter et al 1999;Whangbo and Kenyon 1999;Korswagen 2002;Pan et al 2006) and SPON-1/F-spondin (Josephson et al 2016b), although the Fat-like cadherin CDH-4 has been demonstrated to nonautonomously affect Q-cell migration (Sundararajan et al 2014).…”

Section: Discussionmentioning

confidence: 99%

“…Initial Q migrations are controlled autonomously by the receptor molecules UNC-40/DCC and PTP-3/LAR (Honigberg and Kenyon 2000;Sundararajan and Lundquist 2012) and nonautonomously by the Fat-like cadherin CDH-4 (Sundararajan et al 2014). Later Q-descendant migrations are controlled by Wnt signaling Zinovyeva and Forrester 2005;Zinovyeva et al 2008;Harterink et al 2011), which appears to not be involved in initial migration (Josephson et al 2016a), and by the transmembrane receptor MIG-13 in parallel with SDN-1/Syndecan (Wang et al 2013;Sundararajan et al 2015).…”

mentioning

confidence: 99%

The Caenorhabditis elegans NF2/Merlin Molecule NFM-1 Nonautonomously Regulates Neuroblast Migration and Interacts Genetically with the Guidance Cue SLT-1/Slit

Josephson¹,

Aliani²,

Norris³

et al. 2017

Genetics

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During nervous system development, neurons and their progenitors migrate to their final destinations. In Caenorhabditis elegans, the bilateral Q neuroblasts and their descendants migrate long distances in opposite directions, despite being born in the same posterior region. QR on the right migrates anteriorly and generates the AQR neuron positioned near the head, and QL on the left migrates posteriorly, giving rise to the PQR neuron positioned near the tail. In a screen for genes required for AQR and PQR migration, we identified an allele of nfm-1, which encodes a molecule similar to vertebrate NF2/Merlin, an important tumor suppressor in humans. Mutations in NF2 lead to neurofibromatosis type II, characterized by benign tumors of glial tissues. Here we demonstrate that in C. elegans, nfm-1 is required for the ability of Q cells and their descendants to extend protrusions and to migrate, but is not required for direction of migration. Using a combination of mosaic analysis and cell-specific expression, we show that NFM-1 is required nonautonomously, possibly in muscles, to promote Q lineage migrations. We also show a genetic interaction between nfm-1 and the C. elegans Slit homolog slt-1, which encodes a conserved secreted guidance cue. Our results suggest that NFM-1 might be involved in the generation of an extracellular cue that promotes Q neuroblast protrusion and migration that acts with or in parallel to SLT-1. In vertebrates, NF2 and Slit2 interact in axon pathfinding, suggesting a conserved interaction of NF2 and Slit2 in regulating migratory events.

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“…Neuronal migration also plays important roles in invertebrate nervous systems, including mollusks [11], crustaceans [12], and nematodes [13,14], where the molecular pathways regulating the migratory process can be investigated within intact organisms. Until recently, however, the contribution of migration to the formation of insect nervous systems was under-appreciated.…”

Section: Introduction: Neuronal Migration and The Formation Of The Inmentioning

confidence: 99%

Neuronal migration during development and the amyloid precursor protein

Copenhaver

Ramaker

2016

Current Opinion in Insect Science

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The Amyloid Precursor Protein (APP) is the source of amyloid peptides that accumulate in Alzheimer’s Disease. However, members of the APP family are strongly expressed in the developing nervous systems of invertebrates and vertebrates, where they regulate neuronal guidance, synaptic remodeling, and injury responses. In contrast to mammals, insects express only one APP ortholog (APPL), simplifying investigations into its normal functions. Recent studies have shown that APPL regulates neuronal migration in the developing insect nervous system, analogous to the roles ascribed to APP family proteins in the mammalian cortex. The comparative simplicity of insect systems offers new opportunities for deciphering the signaling mechanisms by which this enigmatic class of proteins contributes to the formation and function of the nervous system.

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SDN-1/Syndecan Acts in Parallel to the Transmembrane Molecule MIG-13 to Promote Anterior Neuroblast Migration

Cited by 20 publications

References 49 publications

Functional Requirements for Heparan Sulfate Biosynthesis in Morphogenesis and Nervous System Development in C. elegans

Functional Requirements for Heparan Sulfate Biosynthesis in Morphogenesis and Nervous System Development in C. elegans

The Caenorhabditis elegans NF2/Merlin Molecule NFM-1 Nonautonomously Regulates Neuroblast Migration and Interacts Genetically with the Guidance Cue SLT-1/Slit

Neuronal migration during development and the amyloid precursor protein

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