Moving around in a worm: netrin UNC-6 and circumferential axon guidance in C. elegans

2002 ◽  
Vol 25 (8) ◽  
pp. 423-429 ◽  
Author(s):  
William G Wadsworth
Keyword(s):  
Axon Guidance ◽  
C Elegans

Identification Of A Novel Gene Altered In The RQ1 Mutant Strain Affecting Motor Axon Migration In Caenorhabditis Elegans

2021 ◽  
Author(s):  
Haider Z. Naqvi
Keyword(s):  
Caenorhabditis Elegans ◽  
Axon Guidance ◽  
Motor Neurons ◽  
Genetic Background ◽  
Germ Line ◽  
Strong Indication ◽  
Wild Type ◽  
C Elegans ◽  
Novel Gene ◽  
Mutation Region

Novel genetic enhancer screens were conducted targeting mutants involved in the guidance of axons of the DA and DB classes of motor neurons in C. elegans. These mutations are expected in genes that function in parallel to the unc-g/Netrin pathway. The screen was conducted in an unc-5(e53) genetic background and enhancers of the axon guidance defects caused by the absence of UNC-5 were identified. Three mutants were previously identified in the screen called rq1, rq2 and rq3 and two additional mutants called H2-4 and M1-3, were isolated in this study. In order to identify the gene affected by the rq1 mutation, wild-type copies of genes in the mapped rq1 mutation region were injected into the mutants to rescue the phenotypic defects. This is a strong indication that the gene of interest is a novel gene called H04D03.1. Promising results indicate that the H04D03.1 protein also works in germ-line apoptosis.

scholarly journals Three C. elegans Rac proteins and several alternative Rac regulators control axon guidance, cell migration and apoptotic cell phagocytosis

Development ◽  
2001 ◽  
Vol 128 (22) ◽  
pp. 4475-4488 ◽  
Author(s):  
Erik A. Lundquist ◽  
Peter W. Reddien ◽  
Erika Hartwieg ◽  
H. Robert Horvitz ◽  
Cornelia I. Bargmann
Keyword(s):  
Cell Migration ◽  
Axon Guidance ◽  
Apoptotic Cell ◽  
Regulatory Proteins ◽  
Axon Pathfinding ◽  
C Elegans ◽  
Cell Corpse ◽  
And Function ◽  
Redundant Functions ◽  
Caenorhabditis Elegans Genome

The Caenorhabditis elegans genome contains three rac-like genes, ced-10, mig-2, and rac-2. We report that ced-10, mig-2 and rac-2 act redundantly in axon pathfinding: inactivating one gene had little effect, but inactivating two or more genes perturbed both axon outgrowth and guidance. mig-2 and ced-10 also have redundant functions in some cell migrations. By contrast, ced-10 is uniquely required for cell-corpse phagocytosis, and mig-2 and rac-2 have only subtle roles in this process. Rac activators are also used differentially. The UNC-73 Trio Rac GTP exchange factor affected all Rac pathways in axon pathfinding and cell migration but did not affect cell-corpse phagocytosis. CED-5 DOCK180, which acts with CED-10 Rac in cell-corpse phagocytosis, acted with MIG-2 but not CED-10 in axon pathfinding. Thus, distinct regulatory proteins modulate Rac activation and function in different developmental processes.

scholarly journals Regulation of axon repulsion by MAX-1 SUMOylation and AP-3

2018 ◽  
Vol 115 (35) ◽  
pp. E8236-E8245
Author(s):  
Shih-Yu Chen ◽  
Chun-Ta Ho ◽  
Wei-Wen Liu ◽  
Mark Lucanic ◽  
Hsiu-Ming Shih ◽  
...  
Keyword(s):  
Axon Guidance ◽  
Neural Development ◽  
Biochemical Analysis ◽  
Genetic Interaction ◽  
Motor Axons ◽  
Surface Receptors ◽  
C Elegans ◽  
Guidance Receptors ◽  
Axon Repulsion

During neural development, growing axons express specific surface receptors in response to various environmental guidance cues. These axon guidance receptors are regulated through intracellular trafficking and degradation to enable navigating axons to reach their targets. In Caenorhabditis elegans, the UNC-5 receptor is necessary for dorsal migration of developing motor axons. We previously found that MAX-1 is required for UNC-5–mediated axon repulsion, but its mechanism of action remained unclear. Here, we demonstrate that UNC-5–mediated axon repulsion in C. elegans motor axons requires both max-1 SUMOylation and the AP-3 complex β subunit gene, apb-3. Genetic interaction studies show that max-1 is SUMOylated by gei-17/PIAS1 and acts upstream of apb-3. Biochemical analysis suggests that constitutive interaction of MAX-1 and UNC-5 receptor is weakened by MAX-1 SUMOylation and by the presence of APB-3, a competitive interactor with UNC-5. Overexpression of APB-3 reroutes the trafficking of UNC-5 receptor into the lysosome for protein degradation. In vivo fluorescence recovery after photobleaching experiments shows that MAX-1 SUMOylation and APB-3 are required for proper trafficking of UNC-5 receptor in the axon. Our results demonstrate that SUMOylation of MAX-1 plays an important role in regulating AP-3–mediated trafficking and degradation of UNC-5 receptors during axon guidance.

scholarly journals Solution Structure of C. elegans UNC-6: A Nematode Paralogue of the Axon Guidance Protein Netrin-1

2019 ◽  
Vol 116 (11) ◽  
pp. 2121-2130 ◽  
Author(s):  
Natalie Krahn ◽  
Markus Meier ◽  
Raphael Reuten ◽  
Manuel Koch ◽  
Joerg Stetefeld ◽  
...  
Keyword(s):  
Axon Guidance ◽  
Solution Structure ◽  
C Elegans

scholarly journals The Nc1/Endostatin Domain of Caenorhabditis elegans Type Xviii Collagen Affects Cell Migration and Axon Guidance

2001 ◽  
Vol 152 (6) ◽  
pp. 1219-1232 ◽  
Author(s):  
Brian D. Ackley ◽  
Jennifer R. Crew ◽  
Harri Elamaa ◽  
Tania Pihlajaniemi ◽  
Calvin J. Kuo ◽  
...  
Keyword(s):  
Cell Migration ◽  
Caenorhabditis Elegans ◽  
Axon Guidance ◽  
Ectopic Expression ◽  
Basement Membranes ◽  
Protein Isoforms ◽  
Developmentally Regulated ◽  
C Elegans ◽  
Collagen Xviii ◽  
Nc1 Domain

Type XVIII collagen is a homotrimeric basement membrane molecule of unknown function, whose COOH-terminal NC1 domain contains endostatin (ES), a potent antiangiogenic agent. The Caenorhabditis elegans collagen XVIII homologue, cle-1, encodes three developmentally regulated protein isoforms expressed predominantly in neurons. The CLE-1 protein is found in low amounts in all basement membranes but accumulates at high levels in the nervous system. Deletion of the cle-1 NC1 domain results in viable fertile animals that display multiple cell migration and axon guidance defects. Particular defects can be rescued by ectopic expression of the NC1 domain, which is shown to be capable of forming trimers. In contrast, expression of monomeric ES does not rescue but dominantly causes cell and axon migration defects that phenocopy the NC1 deletion, suggesting that ES inhibits the promigratory activity of the NC1 domain. These results indicate that the cle-1 NC1/ES domain regulates cell and axon migrations in C. elegans.

scholarly journals Flavin Monooxygenases Regulate C. elegans Axon Guidance and Growth Cone Protrusion with UNC-6/Netrin signaling and Rac GTPases

2017 ◽  
Author(s):  
Mahekta Gujar ◽  
Aubrie M. Stricker ◽  
Erik A. Lundquist
Keyword(s):  
Axon Guidance ◽  
Growth Cone ◽  
Molecular Mechanisms ◽  
Direct Oxidation ◽  
Rac Gtpase ◽  
C Elegans ◽  
Growth Cone Collapse ◽  
Rac Gtpases ◽  
Inhibition Of Growth

AbstractThe guidance cue UNC-6/Netrin regulates both attractive and repulsive axon guidance. Our previous work showed that in C. elegans, the attractive UNC-6/Netrin receptor UNC-40/DCC stimulates growth cone protrusion, and that the repulsive receptor, an UNC-5/UNC-40 heterodimer, inhibits growth cone protrusion. We have also shown that inhibition of growth cone protrusion downstream of the UNC-5/UNC-40 repulsive receptor involves Rac GTPases, the Rac GTP exchange factor UNC-73/Trio, and the cytoskeletal regulator UNC-33/CRMP, which mediates Semaphorin-induced growth cone collapse in other systems. The multidomain flavoprotein monooxygenase (FMO) MICAL also mediates growth cone collapse in response to Semaphorin by directly oxidizing F-actin, resulting in depolymerization. The C. elegans genome does not encode a multidomain MICAL-like molecule, but does encode five flavin monooxygenases (FMO-1, -2, -3, -4, and 5) and another molecule, EHBP-1, similar to the non-FMO portion of MICAL.Here we show that FMO-1, FMO-4, FMO-5, and EHBP-1 may play a role in UNC-6/Netrin directed repulsive guidance mediated through UNC-40 and UNC-5 receptors. Mutations in fmo-1, fmo-4, fmo-5, and ehbp-1 showed VD/DD axon guidance and branching defects, and variably enhanced unc-40 and unc-5 VD/DD guidance defects. Developing growth cones in vivo of fmo-1, fmo-4, fmo-5, and ehbp-1 mutants displayed excessive filopodial protrusion, and transgenic expression of FMO-5 inhibited growth cone protrusion. Mutations suppressed growth cone inhibition caused by activated UNC-40 and UNC-5 signaling, and activated Rac GTPase CED-10 and MIG-2, suggesting that these molecules are required downstream of UNC-6/Netrin receptors and Rac GTPases. From these studies, we conclude that FMO-1, FMO-4, FMO-5, and EHBP-1 represent new players downstream of UNC-6/Netrin receptors and Rac GTPases that inhibit growth cone filopodial protrusion in repulsive axon guidance.Author SummaryMolecular mechanisms of axon repulsion mediated by UNC-6/Netrin are not well understood. Inhibition of growth cone lamellipodial and filopodial protrusion is critical to repulsive axon guidance. Previous work identified a novel pathway involving Rac GTPases and the cytoskeletal interacting molecule UNC-33/CRMP required for UNC-6/Netrin-mediated inhibition of growth cone protrusion. In other systems, CRMP mediates growth cone collapse in response to semaphorin. Here we demonstrate a novel role of flavoprotein monooxygenases (FMOs) in repulsive axon guidance and inhibition of growth cone protrusion downstream of UNC-6/Netrin signaling and Rac GTPases. In Drosophila and vertebrates, the multidomain MICAL FMO mediates semaphorin-dependent growth cone collapse by direct oxidation and depolymerization of F-actin. The C. elegans genome does not encode a multidomain MICAL-like molecule, and we speculate that the C. elegans FMOs might have an equivalent role downstream of UNC-6/Netrin signaling. Indeed, we show that EHBP-1, similar to the non-FMO portion of MICAL, also controls repulsive axon guidance and growth cone inhibition, suggesting that in C. elegans, the functions of the multidomain MICAL molecule might be distributed across different molecules. In sum, we show conservation of function of molecules involved in semaphorin growth cone collapse with inhibition of growth cone protrusion downstream of UNC-6/Netrin signaling.

scholarly journals The Atypical Rho GTPase CHW-1 Works With SAX-3/Robo to Mediate Axon Guidance in Caenorhabditis elegans

2018 ◽  
Author(s):  
Jamie K. Alan ◽  
Sara Robinson ◽  
Katie Magsig ◽  
Rafael S. Demarco ◽  
Erik A. Lundquist
Keyword(s):  
Caenorhabditis Elegans ◽  
Axon Guidance ◽  
Motor Neurons ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Genetic Interaction ◽  
Small Gtpases ◽  
Axon Pathfinding ◽  
Rho Proteins ◽  
C Elegans

AbstractDuring development, neuronal cells extend an axon towards their target destination in response to a cue to form a properly functioning nervous system. Rho proteins, Ras-related small GTPases that regulate cytoskeletal organization and dynamics, cell adhesion, and motility, are known to regulate axon guidance. Despite extensive knowledge about canonical Rho proteins (RhoA/Rac1/Cdc42), little is known about the Caenorhabditis elegans (C. elegans) atypical Cdc42-like family members CHW-1 and CRP-1 in regards to axon pathfinding and neuronal migration. chw-1(Chp/Wrch) encodes a protein that resembles human Chp (Wrch-2/RhoV) and Wrch-1 (RhoU), and crp-1 encodes for a protein that resembles TC10 and TCL. Here, we show that chw-1 works redundantly with crp-1 and cdc-42 in axon guidance. Furthermore, proper levels of chw-1 expression and activity are required for proper axon guidance. When examining CHW-1 GTPase mutants, we found that the native CHW-1 protein is likely partially activated, and mutations at a conserved residue (position 12 using Ras numbering, position 18 in CHW-1) alter axon guidance and neural migration. Additionally, we showed that chw-1 genetically interacts with the guidance receptor sax-3 in PDE neurons. Finally, in VD/DD motor neurons, chw-1 works downstream of sax-3 to control axon guidance. In summary, this is the first study implicating the atypical Rho GTPases chw-1 and crp-1 in axon guidance. Furthermore, this is the first evidence of genetic interaction between chw-1 and the guidance receptor sax-3. These data suggest that chw-1 is likely acting downstream and/or in parallel to sax-3 in axon guidance.

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