Discoidin domain receptors guide axons along longitudinal tracts in C. elegans

Unsoeld, Thomas; Park, Ja-On; Hutter, Harald

doi:10.1016/j.ydbio.2012.11.001

Cited by 25 publications

(28 citation statements)

References 54 publications

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“…For example, we found no correlation between AVK and AVG defects, indicating that AVK defects are not secondary consequences of AVG defects and that AVK navigation is independent of AVG. This is consistent with earlier studies, where defects in AVK axon navigation in the left axon tract were also independent of pioneer defects (Steimel et al 2010;Unsoeld et al 2012). The idea that aex-3 defects are not limited to the VNC pioneer is strengthened by the observation of synergistic effects in aex-3; nid-1 double mutants in commissural navigation, which is completely independent of AVG navigation.…”

Section: Discussionsupporting

confidence: 91%

Pioneer Axon Navigation Is Controlled by AEX-3, a Guanine Nucleotide Exchange Factor for RAB-3 in Caenorhabditis elegans

Bhat¹,

Hutter

2016

Genetics

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Precise and accurate axon tract formation is an essential aspect of brain development. This is achieved by the migration of early outgrowing axons (pioneers) allowing later outgrowing axons (followers) to extend toward their targets in the embryo. In Caenorhabditis elegans the AVG neuron pioneers the right axon tract of the ventral nerve cord, the major longitudinal axon tract. AVG is essential for the guidance of follower axons and hence organization of the ventral nerve cord. In an enhancer screen for AVG axon guidance defects in a nid-1/Nidogen mutant background, we isolated an allele of aex-3. aex-3 mutant animals show highly penetrant AVG axon navigation defects. These defects are dependent on a mutation in nid-1/Nidogen, a basement membrane component. Our data suggest that AEX-3 activates RAB-3 in the context of AVG axon navigation. aex-3 genetically acts together with known players of vesicular exocytosis: unc-64/Syntaxin, unc-31/CAPS, and ida-1/IA-2. Furthermore our genetic interaction data suggest that AEX-3 and the UNC-6/Netrin receptor UNC-5 act in the same pathway, suggesting AEX-3 might regulate the trafficking and/or insertion of UNC-5 at the growth cone to mediate the proper guidance of the AVG axon.

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Section: Discussionsupporting

confidence: 91%

Pioneer Axon Navigation Is Controlled by AEX-3, a Guanine Nucleotide Exchange Factor for RAB-3 in Caenorhabditis elegans

Bhat¹,

Hutter

2016

Genetics

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“…There are two genes that encode DDRs in C . elegans , DDR-1 and DDR-2 (Fig 1B) [10]. They display a similar topology to the human homologs, with an extracellular region containing the ligand-binding discoidin domain, a single transmembrane region, and a cytoplasmic region which contains a tyrosine kinase domain.…”

Section: Resultsmentioning

confidence: 99%

The C. elegans Discoidin Domain Receptor DDR-2 Modulates the Met-like RTK–JNK Signaling Pathway in Axon Regeneration

et al. 2016

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The ability of specific neurons to regenerate their axons after injury is governed by cell-intrinsic regeneration pathways. However, the signaling pathways that orchestrate axon regeneration are not well understood. In Caenorhabditis elegans, initiation of axon regeneration is positively regulated by SVH-2 Met-like growth factor receptor tyrosine kinase (RTK) signaling through the JNK MAPK pathway. Here we show that SVH-4/DDR-2, an RTK containing a discoidin domain that is activated by collagen, and EMB-9 collagen type IV regulate the regeneration of neurons following axon injury. The scaffold protein SHC-1 interacts with both DDR-2 and SVH-2. Furthermore, we demonstrate that overexpression of svh-2 and shc-1 suppresses the delay in axon regeneration observed in ddr-2 mutants, suggesting that DDR-2 functions upstream of SVH-2 and SHC-1. These results suggest that DDR-2 modulates the SVH-2–JNK pathway via SHC-1. We thus identify two different RTK signaling networks that play coordinated roles in the regulation of axonal regeneration.

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“…cle-1 mutants have defects in the organization and function of synapses but only a few minor defects in axonal navigation have been described (Ackley et al 2001(Ackley et al , 2003. Mutations in a putative receptor for collagens, ddr-2, cause navigation defects in the VNC and other longitudinal axon tracts (Unsoeld et al 2013), implying a role for one or more collagens in axon navigation. None of the characterized collagens share the ddr-2 defects, so the ligand DDR-2 remains unclear.…”

Section: Basement Membrane Proteinsmentioning

confidence: 99%

“…These include basement membrane components such as UNC-52 (perlecan), NID-1 (nidogen), and CLE-1 (type XVIII collagen); and receptors such as DDR-1 and DDR-2 (discoidin domain receptors), DGN-1 (dystroglycan), and UNC-71 (ADAM) (Kim and Wadsworth 2000;Ackley et al 2001;X. Huang et al 2003;Johnson and Kramer 2012;Unsoeld et al 2013). These molecules can regulate axonal outgrowth activity when there are contactspecific extracellular matrices, tissues, or cells, thereby changing outgrowth behavior at specific locations.…”

Section: Orienting Outgrowth Activity To the Extracellular Environmentmentioning

confidence: 99%

“…The development and sorting of axons into specific tracts is achieved by the outgrowth responses that pioneer and follower axons have to the combination of cues expressed by the surrounding environment and by each other (Hutter 2003). At present only a few molecules are known to be involved in this sorting process, including NID-1 (nidogen), FMI-1 (flamingo), , and the discoidin domain receptors, DDR-1 and DDR-2 (Steimel et al 2010;Unsoeld et al 2013).…”

Section: Models Of Axon Guidancementioning

confidence: 99%

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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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Discoidin domain receptors guide axons along longitudinal tracts in C. elegans

Cited by 25 publications

References 54 publications

Pioneer Axon Navigation Is Controlled by AEX-3, a Guanine Nucleotide Exchange Factor for RAB-3 in Caenorhabditis elegans

Pioneer Axon Navigation Is Controlled by AEX-3, a Guanine Nucleotide Exchange Factor for RAB-3 in Caenorhabditis elegans

The C. elegans Discoidin Domain Receptor DDR-2 Modulates the Met-like RTK–JNK Signaling Pathway in Axon Regeneration

The Genetics of Axon Guidance and Axon Regeneration in Caenorhabditis elegans

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