Glypican Is a Modulator of Netrin-Mediated Axon Guidance

Blanchette, Cassandra R.; Perrat, Paola N.; Thackeray, Andrea; Bénard, Claire

doi:10.1371/journal.pbio.1002183

Cited by 57 publications

(85 citation statements)

References 62 publications

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“…Despite these observations, our lon-2 loss-of-function data are robust and continue to support a role for LON-2 during AIY primary neurite outgrowth and branching. This is consistent with previous work demonstrating partly redundant roles for LON-2 in nervous system development, including genetic and physical interactions between LON-2 and the axon guidance molecules UNC-40/DCC and UNC-6/ netrin (Díaz-Balzac et al 2014;Kinnunen 2014;Blanchette et al 2015).…”

Section: Sdn-1 and Glypicans Have Opposing Roles In Both Primary Neursupporting

confidence: 93%

“…In C. elegans, the single-pass trans-membrane HSPG SDN-1/ syndecan is required for neuroblast migration, axon outgrowth, axon guidance, and post-embryonic cell migration in multiple C. elegans CNS cell types (Rhiner et al 2005;Hudson et al 2006;Díaz-Balzac et al 2014;Kinnunen 2014). In addition, LON-2/glypican has roles in the left/right guidance choices of dorsal B-type (DB) motor neurons and other axon guidance events (Bülow et al 2008;Gysi et al 2013;Pedersen et al 2013;Díaz-Balzac et al 2014;Blanchette et al 2015). GPN-1/glypican is redundantly required for embryonic neuroblast migration but has no other reported function in C. elegans development (Hudson et al 2006).…”

Section: Efn-4 Acts Non-cell Autonomously To Promote Aiy Outgrowth Anmentioning

confidence: 99%

“…This phenotype is strongly suppressed by mutations in HS modification enzymes, and in vitro binding studies have confirmed that KAL-1 can bind the HSPGs sdn-1/syndecan and gpn-1/glypican (Bülow et al 2002;Hudson et al 2006;Tornberg et al 2011). HSPGs are required for many aspects of nervous system development in both vertebrates and invertebrates, including cell migration, axon guidance, and synaptogenesis (Rhiner et al 2005;Van Vactor et al 2006;Gysi et al 2013;Kinnunen 2014;Blanchette et al 2015). Considering the importance of both HSPGs and Eph/ephrin signaling during nervous system development, surprisingly little research has been dedicated to possible interactions between these pathways (Irie et al 2008;Holen et al 2011).…”

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confidence: 97%

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The Caenorhabditis elegans Ephrin EFN-4 Functions Non-cell Autonomously with Heparan Sulfate Proteoglycans to Promote Axon Outgrowth and Branching

et al. 2015

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The Eph receptors and their cognate ephrin ligands play key roles in many aspects of nervous system development. These interactions typically occur within an individual tissue type, serving either to guide axons to their terminal targets or to define boundaries between the rhombomeres of the hindbrain. We have identified a novel role for the Caenorhabditis elegans ephrin EFN-4 in promoting primary neurite outgrowth in AIY interneurons and D-class motor neurons. Rescue experiments reveal that EFN-4 functions non-cell autonomously in the epidermis to promote primary neurite outgrowth. We also find that EFN-4 plays a role in promoting ectopic axon branching in a C. elegans model of X-linked Kallmann syndrome. In this context, EFN-4 functions non-cell autonomously in the body-wall muscle and in parallel with HS modification genes and HSPG core proteins. This is the first report of an epidermal ephrin providing a developmental cue to the nervous system. KEYWORDS ephrin; Eph receptor; heparan sulfate proteoglycan; axon outgrowth; axon branching A CCURATE development of the central nervous system requires contributions both from the extracellular environment in the form of guidepost cues and secreted guidance molecules and from contact with adjacent neurons or other tissues in the form of cell-surface receptors that can detect and transduce navigation cues. Guideposts typically take the form of specific tissue types such as the ventral midline of Caenorhabditis elegans or Drosophila, which provides a permissive environment for neurons to migrate along, while secreted guidance molecules provide spatial information and navigation instructions in the form of repulsive or attractive cues (Chilton 2006;Killeen and Sybingco 2008). Many studies have identified how individual neurons and guidance cues act to provide spatial and navigation information, but how does a single cell that possesses multiple axon guidance receptors find its target when exposed to multiple guidance cues? The nervous system of the nematode C. elegans provides a simple and defined model to examine the interplay between multiple neuronal guidance systems. The morphology and connectivity of C. elegans neurons have been established by serial-section electron microscopy, and the C. elegans genome possesses orthologs of most vertebrate axon guidance and guidepost genes (White et al. 1986;Bargmann 1998;Chisholm and Jin 2005;Ackley 2014). One of the most important classes of axon guidance molecules is the Eph receptor tyrosine kinases and their cognate ligands, the ephrins (Flanagan 2006;Lisabeth et al. 2013;Cayuso et al. 2015). Eph receptors and ephrins are required for the accurate connectivity of many parts of the vertebrate brain and also have roles in cell adhesion and embryonic morphogenesis (George et al. 1998;Chin-Sang et al. 1999;Chin-Sang et al. 2002;Klein 2012). We previously showed that the C. elegans ephrin EFN-4 functions in concert with the KAL-1/anosmin-heparan sulfate proteoglycan (HSPG) pathway to regulate neuroblast migration during...

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Section: Sdn-1 and Glypicans Have Opposing Roles In Both Primary Neursupporting

confidence: 93%

Section: Efn-4 Acts Non-cell Autonomously To Promote Aiy Outgrowth Anmentioning

confidence: 99%

mentioning

confidence: 97%

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The Caenorhabditis elegans Ephrin EFN-4 Functions Non-cell Autonomously with Heparan Sulfate Proteoglycans to Promote Axon Outgrowth and Branching

et al. 2015

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“…A function of the core protein LON-2 independent of sugar modifications was also observed during ventral migration of the AVM axons. lon-2 mutants alone show no defects, but enhance defects in sdn-1 mutants in this case (Blanchette et al 2015). Genetic interaction data and binding studies in cell culture indicate that LON-2 modulates responses to UNC-6 (netrin) by interacting directly or indirectly with the UNC-6 receptor UNC-40 (DCC) (Blanchette et al 2015).…”

Section: Heparan Sulfate Proteoglycansmentioning

confidence: 94%

“…lon-2 mutants alone show no defects, but enhance defects in sdn-1 mutants in this case (Blanchette et al 2015). Genetic interaction data and binding studies in cell culture indicate that LON-2 modulates responses to UNC-6 (netrin) by interacting directly or indirectly with the UNC-6 receptor UNC-40 (DCC) (Blanchette et al 2015). kal-1 encodes the C. elegans ortholog of the Kallmann syndrome protein Anosmin-1.…”

Section: Heparan Sulfate Proteoglycansmentioning

confidence: 99%

The Genetics of Axon Guidance and Axon Regeneration in Caenorhabditis elegans

Chisholm¹,

Hutter

Jin

et al. 2016

Genetics

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The correct wiring of neuronal circuits depends on outgrowth and guidance of neuronal processes during development. In the past two decades, great progress has been made in understanding the molecular basis of axon outgrowth and guidance. Genetic analysis in Caenorhabditis elegans has played a key role in elucidating conserved pathways regulating axon guidance, including Netrin signaling, the slit Slit/Robo pathway, Wnt signaling, and others. Axon guidance factors were first identified by screens for mutations affecting animal behavior, and by direct visual screens for axon guidance defects. Genetic analysis of these pathways has revealed the complex and combinatorial nature of guidance cues, and has delineated how cues guide growth cones via receptor activity and cytoskeletal rearrangement. Several axon guidance pathways also affect directed migrations of non-neuronal cells in C. elegans, with implications for normal and pathological cell migrations in situations such as tumor metastasis. The small number of neurons and highly stereotyped axonal architecture of the C. elegans nervous system allow analysis of axon guidance at the level of single identified axons, and permit in vivo tests of prevailing models of axon guidance. C. elegans axons also have a robust capacity to undergo regenerative regrowth after precise laser injury (axotomy). Although such axon regrowth shares some similarities with developmental axon outgrowth, screens for regrowth mutants have revealed regenerationspecific pathways and factors that were not identified in developmental screens. Several areas remain poorly understood, including how major axon tracts are formed in the embryo, and the function of axon regeneration in the natural environment. KEYWORDS netrin; semaphorin; ephrin; Wnt; Slit; Robo; fasciculation; DLK; growth cone; actin; microtubule; WormBook

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Cooperation and crosstalk in axon guidance cue integration: Additivity, synergy, and fine‐tuning in combinatorial signaling

Morales

Kania

2016

Developmental Neurobiology

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Neural circuit development involves the coordinated growth and guidance of axons to their targets. Following the identification of many guidance cue molecules, recent experiments have focused on the interactions of their signaling cascades, which can be generally classified as additive or non-additive depending on the signal convergence point. While additive (parallel) signaling suggests limited molecular interaction between the pathways, non-additive signaling involves crosstalk between pathways and includes more complex synergistic, hierarchical, and permissive guidance cue relationships. Here the authors have attempted to classify recent studies that describe axon guidance signal integration according to these divisions. They also discuss the mechanistic implications of such interactions, as well as general ideas relating signal integration to the generation of diversity of axon guidance responses. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 891-904, 2017.

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Glypican Is a Modulator of Netrin-Mediated Axon Guidance

Cited by 57 publications

References 62 publications

The Caenorhabditis elegans Ephrin EFN-4 Functions Non-cell Autonomously with Heparan Sulfate Proteoglycans to Promote Axon Outgrowth and Branching

The Caenorhabditis elegans Ephrin EFN-4 Functions Non-cell Autonomously with Heparan Sulfate Proteoglycans to Promote Axon Outgrowth and Branching

The Genetics of Axon Guidance and Axon Regeneration in Caenorhabditis elegans

Cooperation and crosstalk in axon guidance cue integration: Additivity, synergy, and fine‐tuning in combinatorial signaling

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