The genetics of axon guidance and axon regeneration in caenorhabditis elegans

Genetics

Volumn 204, Issue 3, 2016, Pages 849-882

  Chisholm, Andrew D ^a   Hutter, Harald ^c   Jin, Yishi ^a,b,d   Wadsworth, William G ^e  

^a NEUROBIOLOGY SECTION   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c SIMON FRASER UNIVERSITY   (Canada)

^d HOWARD HUGHES MEDICAL INSTITUTE   (United States)

^e RUTGERS ROBERT WOOD JOHNSON MEDICAL SCHOOL   (United States)

Author keywords

Actin; DLK; Ephrin; Fasciculation; Growth cone; Microtubule; Netrin; Robo; Semaphorin; Slit; Wnt; WormBook

Indexed keywords

INSULIN; INTEGRIN RECEPTOR; MICRORNA; PHOSPHOTRANSFERASE; PROTEOHEPARAN SULFATE;

ACTIN FILAMENT; ARTICLE; AXON; AXONAL INJURY; BASEMENT MEMBRANE; CAENORHABDITIS ELEGANS; GENE EXPRESSION; GENE MUTATION; GENETICS; GROWTH CONE; MOLECULAR DYNAMICS; NERVE FIBER GROWTH; NERVE FIBER REGENERATION; NONHUMAN; PRIORITY JOURNAL; RNA PROCESSING; SECOND MESSENGER; SIGNAL TRANSDUCTION; ANIMAL; AXON GUIDANCE; GROWTH, DEVELOPMENT AND AGING; METABOLISM; NERVE REGENERATION; PHYSIOLOGY;

ACTIN CYTOSKELETON; ANIMALS; AXON GUIDANCE; CAENORHABDITIS ELEGANS; NERVE REGENERATION;

EID: 84994910642     PISSN: 00166731     EISSN: 19432631     Source Type: Journal    
DOI: 10.1534/genetics.115.186262     Document Type: Article

References (304)

1. Ackley, B. D., J. R. Crew, H. Elamaa, T. Pihlajaniemi, C. J. Kuo et al., 2001 The NC1/endostatin domain of Caenorhabditis elegans type XVIII collagen affects cell migration and axon guidance. J. Cell Biol. 152: 1219–1232.
2. Ackley, B. D., S. H. Kang, J. R. Crew, C. Suh, Y. Jin et al., 2003 The basement membrane components nidogen and type XVIII collagen regulate organization of neuromuscular junctions in Caenorhabditis elegans. J. Neurosci. 23: 3577–3587.
3. Adler, C. E., R. D. Fetter, and C. I. Bargmann, 2006 UNC-6/Netrin induces neuronal asymmetry and defines the site of axon formation. Nat. Neurosci. 9: 511–518.
4. Alam, T., H. Maruyama, C. Li, S. I. Pastuhov, P. Nix et al., 2016 Axotomy-induced HIF-serotonin signalling axis promotes axon regeneration in C. elegans. Nat. Commun. 7: 10388.
5. Alexander, M., K. K. Chan, A. B. Byrne, G. Selman, T. Lee et al., 2009 An UNC-40 pathway directs postsynaptic membrane extension in Caenorhabditis elegans. Development 136: 911–922.
6. Alexander, M., G. Selman, A. Seetharaman, K. K. Chan, S. A. D’Souza et al., 2010 MADD-2, a homolog of the Opitz syndrome protein MID1, regulates guidance to the midline through UNC-40 in Caenorhabditis elegans. Dev. Cell 18: 961–972.
7. Altun, Z. F., and D. H. Hall, 2011 Nervous system, general description, in WormAtlas, edited for the web by Herndon, L. A. In WormAtlas. DOI:10.3908/wormatlas.1.18. Last revision: June 19, 2013.
8. Andrusiak, M. G., and Y. Jin, 2016 Context specificity of stress-activated mitogen-activated protein (MAP) kinase signaling: the story as told by Caenorhabditis elegans. J. Biol. Chem. 291: 7796–7804.
9. Asakura, T., K. Ogura, and Y. Goshima, 2007 UNC-6 expression by the vulval precursor cells of Caenorhabditis elegans is required for the complex axon guidance of the HSN neurons. Dev. Biol. 304: 800–810.
10. Asan, A., S. A. Raiders, and J. R. Priess, 2016 Morphogenesis of the C. elegans intestine involves axon guidance genes. PLoS Genet. 12: e1005950.
11. Aurelio, O., D. H. Hall, and O. Hobert, 2002 Immunoglobulin-domain proteins required for maintenance of ventral nerve cord organization. Science 295: 686–690.
12. Bader, B. L., N. Smyth, S. Nedbal, N. Miosge, A. Baranowsky et al., 2005 Compound genetic ablation of nidogen 1 and 2 causes basement membrane defects and perinatal lethality in mice. Mol. Cell. Biol. 25: 6846–6856.
13. Baird, S. E., D. H. Fitch, I. A. Kassem, and S. W. Emmons, 1991 Pattern formation in the nematode epidermis: determination of the arrangement of peripheral sense organs in the C. elegans male tail. Development 113: 515–526.
14. Baum, P. D., and G. Garriga, 1997 Neuronal migrations and axon fasciculation are disrupted in ina-1 integrin mutants. Neuron 19: 51–62.
15. Bénard, C. Y., C. Blanchette, J. Recio, and O. Hobert, 2012 The secreted immunoglobulin domain proteins ZIG-5 and ZIG-8 cooperate with L1CAM/SAX-7 to maintain nervous system integrity. PLoS Genet. 8: e1002819.
16. Bernadskaya, Y. Y., A. Wallace, J. Nguyen, W. A. Mohler, and M. C. Soto, 2012 UNC-40/DCC, SAX-3/Robo, and VAB-1/Eph polarize F-actin during embryonic morphogenesis by regulating the WAVE/SCAR actin nucleation complex. PLoS Genet. 8: e1002863.
17. Bhat, J. M., and H. Hutter, 2016 Pioneer axon navigation is controlled by AEX-3, a guanine nucleotide exchange factor for RAB-3 in Caenorhabditis elegans. Genetics 203: 1235–1247.
18. Bhat, J. M., J. Pan, and H. Hutter, 2015 PLR-1, a putative E3 ubiquitin ligase, controls cell polarity and axonal extensions in C. elegans. Dev. Biol. 398: 44–56.
19. Blanchette, C. R., P. N. Perrat, A. Thackeray, and C. Y. Bénard, 2015 Glypican is a modulator of netrin-mediated axon guidance. PLoS Biol. 13: e1002183.
20. Blelloch, R., S. S. Anna-Arriola, D. Gao, Y. Li, J. Hodgkin et al., 1999 The gon-1 gene is required for gonadal morphogenesis in Caenorhabditis elegans. Dev. Biol. 216: 382–393.
21. Boulin, T., R. Pocock, and O. Hobert, 2006 A novel Eph receptor-interacting IgSF protein provides C. elegans motoneurons with midline guidepost function. Curr. Biol. 16: 1871–1883.
22. Bounoutas, A., J. Kratz, L. Emtage, C. Ma, K.C. Nguyen et al., 2011 Microtubule depolymerization in Caenorhabditis elegans touch receptor neurons reduces gene expression through a p38 MAPK pathway. Proc. Natl. Acad. Sci. USA 108: 3982– 3987.
23. Bradke, F., J. W. Fawcett, and M. E. Spira, 2012 Assembly of a new growth cone after axotomy: the precursor to axon regeneration. Nat. Rev. Neurosci. 13: 183–193.
24. Brenner, S., 1974 The genetics of Caenorhabditis elegans. Genetics 77: 71–94.
25. Broadbent, I. D., and J. Pettitt, 2002 The C. elegans hmr-1 gene can encode a neuronal classic cadherin involved in the regulation of axon fasciculation. Curr. Biol. 12: 59–63.
26. Bülow, H. E., and O. Hobert, 2004 Differential sulfations and epi-merization define heparan sulfate specificity in nervous system development. Neuron 41: 723–736.
27. Bülow, H. E., K. L. Berry, L. H. Topper, E. Peles, and O. Hobert, 2002 Heparan sulfate proteoglycan-dependent induction of axon branching and axon misrouting by the Kallmann syndrome gene kal-1. Proc. Natl. Acad. Sci. USA 99: 6346–6351.
28. Bülow, H. E., N. Tjoe, R. A. Townley, D. Didiano, T. H. van Kuppevelt et al., 2008 Extracellular sugar modifications provide instructive and cell-specific information for axon-guidance choices. Curr. Biol. 18: 1978–1985.
29. Byrne, A. B., T. Walradt, K. E. Gardner, A. Hubbert, V. Reinke et al., 2014 Insulin/IGF1 signaling inhibits age-dependent axon regeneration. Neuron 81: 561–573.
30. Cang, J., and D. A. Feldheim, 2013 Developmental mechanisms of topographic map formation and alignment. Annu. Rev. Neurosci. 36: 51–77.
31. Chan, K. K., A. Seetharaman, R. Bagg, G. Selman, Y. Zhang et al., 2014 EVA-1 functions as an UNC-40 co-receptor to enhance attraction to the MADD-4 guidance cue in Caenorhabditis elegans. PLoS Genet. 10: e1004521.
32. Chan, S. S., H. Zheng, M. W. Su, R. Wilk, M. T. Killeen et al., 1996 UNC-40, a C. elegans homolog of DCC (Deleted in Colorectal Cancer), is required in motile cells responding to UNC-6 netrin cues. Cell 87: 187–195.
33. Chang, C., C. E. Adler, M. Krause, S. G. Clark, F. B. Gertler et al., 2006 MIG-10/Lamellipodin and AGE-1/PI3K promote axon guidance and outgrowth in response to slit and netrin. Curr. Biol. 16: 854–862.
34. Chedotal, A., G. Kerjan, and C. Moreau-Fauvarque, 2005 The brain within the tumor: new roles for axon guidance molecules in cancers. Cell Death Differ. 12: 1044–1056.
35. Chen, L., Z. Wang, A. Ghosh-Roy, T. Hubert, D. Yan et al., 2011 Axon regeneration pathways identified by systematic genetic screening in C. elegans. Neuron 71: 1043–1057.
36. Chen, L., M. Chuang, T. Koorman, M. Boxem, Y. Jin et al., 2015 Axon injury triggers EFA-6 mediated destabilization of axonal microtubules via TACC and doublecortin like kinase. eLife 4: e08695.
37. Chin-Sang, I. D., S. E. George, M. Ding, S. L. Moseley, A. S. Lynch et al., 1999 The ephrin VAB-2/EFN-1 functions in neuronal signaling to regulate epidermal morphogenesis in C. elegans. Cell 99: 781–790.
38. Chin-Sang, I. D., S. L. Moseley, M. Ding, R. J. Harrington, S. E. George et al., 2002 The divergent C. elegans ephrin EFN-4 functions inembryonic morphogenesis in a pathway independent of the VAB-1 Eph receptor. Development 129: 5499–5510.
39. Chisholm, A. D., 2013 Cytoskeletal dynamics in Caenorhabditis elegans axon regeneration. Annu. Rev. Cell Dev. Biol. 29: 271–297.
40. Chisholm, A., and M. Tessier-Lavigne, 1999 Conservation and divergence of axon guidance mechanisms. Curr. Opin. Neurobiol. 9: 603–615.
41. Cho, Y., J. E. Shin, E. E. Ewan, Y. M. Oh, W. Pita-Thomas et al., 2015 Activating injury-responsive genes with hypoxia enhances axon regeneration through neuronal HIF-1alpha. Neuron 88: 720–734.
42. Christensen, R., L. de la Torre-Ubieta, A. Bonni, and D. A. Colon-Ramos, 2011 A conserved PTEN/FOXO pathway regulates neuronal morphology during C. elegans development. Development 138: 5257–5267.
43. Christensen, R. P., A. Bokinsky, A. Santella, Y. Wu, J. Marquina-Solis et al., 2015 Untwisting the Caenorhabditis elegans embryo. eLife 4: .10.7554/eLife.10070
44. Chuang, M., A. Goncharov, S. Wang, K. Oegema, Y. Jin et al., 2014 The microtubule minus end binding protein Patronin/ PTRN-1 is required for axon regeneration in C. elegans. Cell Reports 9: 874–883.
45. Chung, S. H., D. A. Clark, C. V. Gabel, E. Mazur, and A. D. Samuel, 2006 The role of the AFD neuron in C. elegans thermotaxis analyzed using femtosecond laser ablation. BMC Neurosci. 7: 30.
46. Chung, S. H., M. R. Awal, J. Shay, M. M. McLoed, E. Mazur et al., 2016 Novel DLK-independent neuronal regeneration in Caenorhabditis elegans shares links with activity-dependent ectopic outgrowth. Proc. Natl. Acad. Sci. USA 113: E2852–E2860.
47. Clark, S. G., and C. Chiu, 2003 C. elegans ZAG-1, a Zn-finger-homeodomain protein, regulates axonal development and neuronal differentiation. Development 130: 3781–3794.
48. Colavita, A., and J. G. Culotti, 1998 Suppressors of ectopic UNC-5 growth cone steering identify eight genes involved in axon guidance in Caenorhabditis elegans. Dev. Biol. 194: 72–85.
49. Colavita, A., S. Krishna, H. Zheng, R. W. Padgett, and J. G. Culotti, 1998 Pioneer axon guidance by UNC-129, a C. elegans TGF-beta. Science 281: 706–709.
50. Colon-Ramos, D. A., M. A. Margeta, and K. Shen, 2007 Glia promote local synaptogenesis through UNC-6 (netrin) signaling in C. elegans. Science 318: 103–106.
51. Dai, Y., H. Taru, S. L. Deken, B. Grill, B. Ackley et al., 2006 SYD-2 Liprin-alpha organizes presynaptic active zone formation through ELKS. Nat. Neurosci. 9: 1479–1487.
52. Demarco, R. S., and E. A. Lundquist, 2010 RACK-1 acts with Rac GTPase signaling and UNC-115/abLIM in Caenorhabditis elegans axon pathfinding and cell migration. PLoS Genet. 6: e1001215.
53. Demarco, R. S., E. C. Struckhoff, and E. A. Lundquist, 2012 The Rac GTP exchange factor TIAM-1 acts with CDC-42 and the guidance receptor UNC-40/DCC in neuronal protrusion and axon guidance. PLoS Genet. 8: e1002665.
54. Dent, E. W., S. L. Gupton, and F. B. Gertler, 2011 The growth cone cytoskeleton in axon outgrowth and guidance. Cold Spring Harb. Perspect. Biol. 3: pii: a001800.
55. Díaz-Balzac, C. A., M. I. Lázaro-Peña, E. Tecle, N. Gomez, and H. E. Bülow, 2014 Complex cooperative functions of heparan sulfate proteoglycans shape nervous system development in Caenorhabditis elegans. G3 (Bethesda) 4: 1859–1870.
56. Díaz-Balzac, C. A., M. I. Lázaro-Peña, G. A. Ramos-Ortiz, and H. E. Bülow, 2015 The adhesion molecule KAL-1/anosmin-1 regulates neurite branching through a SAX-7/L1CAM-EGL-15/FGFR receptor complex. Cell Reports 11: 1377–1384.
57. Dickson, B. J., and Y. Zou, 2010 Navigating intermediate targets: the nervous system midline. Cold Spring Harb. Perspect. Biol. 2: a002055.
58. Dong, B., M. Moseley-Alldredge, A. A. Schwieterman, C. J. Donelson, J. L. McMurry et al., 2016 EFN-4 functions in LAD-2-mediated axon guidance in Caenorhabditis elegans. Development 143: 1182–1191.
59. Dong, X., K. Shen, and H. E. Bülow, 2015 Intrinsic and extrinsic mechanisms of dendritic morphogenesis. Annu. Rev. Physiol. 77: 271–300.
60. Durbin, R., 1987 Studies on the development and organisation of the nervous system of Caenorhabditis elegans. Ph.D. Thesis, University of Cambridge.
61. Edwards, D. R., M. M. Handsley, and C. J. Pennington, 2008 The ADAM metalloproteinases. Mol. Aspects Med. 29: 258–289.
62. Edwards,S.L.,L.M.Morrison,R.M.Yorks,C.M.Hoover,S.Boominathan et al., 2015a UNC-16 (JIP3) acts through synapse-assembly proteins to inhibit the active transport of cell soma organelles to Caenorhabditis elegans motor neuron axons. Genetics 201: 117–141.
63. Edwards, S. L., R. M. Yorks, L. M. Morrison, C. M. Hoover, and K. G. Miller, 2015b Synapse-assembly proteins maintain synaptic vesicle cluster stability and regulate synaptic vesicle transport in Caenorhabditis elegans. Genetics 201: 91–116.
64. Edwards, T. J., and M. Hammarlund, 2014 Syndecan promotes axon regeneration by stabilizing growth cone migration. Cell Reports 8: 272–283.
65. El Bejjani, R., and M. Hammarlund, 2012 Neural regeneration in Caenorhabditis elegans. Annu. Rev. Genet. 46: 499–513.
66. Fleming,T.,S.C.Chien,P.J.Vanderzalm,M.Dell,M.K.Gavin et al., 2010 The role of C. elegans Ena/VASP homolog UNC-34 in neuronal polarity and motility. Dev. Biol. 344: 94–106.
67. Forrester, W. C., and G. Garriga, 1997 Genes necessary for C. elegans cell and growth cone migrations. Development 124: 1831–1843.
68. Fujisawa, K., J. L. Wrana, and J. G. Culotti, 2007 The slit receptor EVA-1 coactivates a SAX-3/Robo mediated guidance signal in C. elegans. Science 317: 1934–1938.
69. Gabel, C. V., F. Antoine, C. F. Chuang, A. D. Samuel, and C. Chang, 2008 Distinct cellular and molecular mechanisms mediate initial axon development and adult-stage axon regeneration in C. elegans. Development 135: 1129–1136.
70. Garriga, G., C. Desai, and H. R. Horvitz, 1993 Cell interactions control the direction of outgrowth, branching and fasciculation of the HSN axons of Caenorhabditis elegans. Development 117: 1071–1087.
71. Geoffroy, C. G., and B. Zheng, 2014 Myelin-associated inhibitors in axonal growth after CNS injury. Curr. Opin. Neurobiol. 27: 31–38.
72. George, S. E., K. Simokat, J. Hardin, and A. D. Chisholm, 1998 The VAB-1 Eph receptor tyrosine kinase functions in neural and epithelial morphogenesis in C. elegans. Cell 92: 633–643.
73. Gettner, S. N., C. Kenyon, and L. F. Reichardt, 1995 Characterization of beta pat-3 heterodimers, a family of essential integrin receptors in C. elegans. J. Cell Biol. 129: 1127–1141.
74. Ghosh-Roy, A., Z. Wu, A. Goncharov, Y. Jin, and A. D. Chisholm, 2010 Calcium and cyclic AMP promote axonal regeneration in Caenorhabditis elegans and require DLK-1 kinase. J. Neurosci. 30: 3175–3183.
75. Ghosh-Roy, A., A. Goncharov, Y. Jin, and A. D. Chisholm, 2012 Kinesin-13 and tubulin posttranslational modifications regulate microtubule growth in axon regeneration. Dev. Cell 23: 716–728.
76. Giger, R. J., E. R. Hollis, II, and M. H. Tuszynski, 2010 Guidance molecules in axon regeneration. Cold Spring Harb. Perspect. Biol. 2: a001867.
77. Ginzburg, V. E., P. J. Roy, and J. G. Culotti, 2002 Semaphorin 1a and semaphorin 1b are required for correct epidermal cell positioning and adhesion during morphogenesis in C. elegans. Development 129: 2065–2078.
78. Gitai, Z., T. W. Yu, E. A. Lundquist, M. Tessier-Lavigne, and C. I. Bargmann, 2003 The netrin receptor UNC-40/DCC stimulates axon attraction and outgrowth through enabled and, in parallel, Rac and UNC-115/AbLIM. Neuron 37: 53–65.
79. Gokce, S. K., S. X. Guo, N. Ghorashian, W. N. Everett, T. Jarrell et al., 2014 A fully automated microfluidic femtosecond laser axotomy platform for nerve regeneration studies in C. elegans. PLoS One 9: e113917.
80. Gotenstein, J. R., R. E. Swale, T. Fukuda, Z. Wu, C. A. Giurumescu et al., 2010 The C. elegans peroxidasin PXN-2 is essential for embryonic morphogenesis and inhibits adult axon regeneration. Development 137: 3603–3613.
81. Grill, B., R. K. Murphey, and M. A. Borgen, 2016 The PHR proteins: intracellular signaling hubs in neuronal development and axon degeneration. Neural Dev. 11: 8.
82. Grossman, E. N., C. A. Giurumescu, and A. D. Chisholm, 2013 Mechanisms of ephrin receptor protein kinase-independent signaling in amphid axon guidance in Caenorhabditis elegans. Genetics 195: 899–913.
83. Guo, S. X., F. Bourgeois, T. Chokshi, N. J. Durr, M. A. Hilliard et al., 2008 Femtosecond laser nanoaxotomy lab-on-a-chip for in vivo nerve regeneration studies. Nat. Methods 5: 531–533.
84. Gysi, S., C. Rhiner, S. Flibotte, D. G. Moerman, and M. O. Hengartner, 2013 A network of HSPG core proteins and HS modifying enzymes regulates netrin-dependent guidance of D-type motor neurons in Caenorhabditis elegans. PLoS One 8: e74908.
85. Hagedorn, E. J., and D. R. Sherwood, 2011 Cell invasion through basement membrane: the anchor cell breaches the barrier. Curr. Opin. Cell Biol. 23: 589–596.
86. Hagedorn, E. J., H. Yashiro, J. W. Ziel, S. Ihara, Z. Wang et al., 2009 Integrin acts upstream of netrin signaling to regulate formation of the anchor cell’s invasive membrane in C. elegans. Dev. Cell 17: 187–198.
87. Hagedorn, E. J., J. W. Ziel, M. A. Morrissey, L. M. Linden, Z. Wang et al., 2013 The netrin receptor DCC focuses invadopodia-driven basement membrane transmigration in vivo. J. Cell Biol. 201: 903–913.
88. Hahn, A. C., and S. W. Emmons, 2003 The roles of an ephrin and a semaphorin in patterning cell-cell contacts in C. elegans sensory organ development. Dev. Biol. 256: 379–388.
89. Hall, D. H., and Z. F. Altun, 2008 C. elegans Atlas. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
90. Hallam, S. J., A. Goncharov, J. McEwen, R. Baran, and Y. Jin, 2002 SYD-1, a presynaptic protein with PDZ, C2 and rho-GAP-like domains, specifies axon identity in C. elegans. Nat. Neurosci. 5: 1137–1146.
91. Hamelin, M., Y. Zhou, M. W. Su, I. M. Scott, and J. G. Culotti, 1993 Expression of the UNC-5 guidance receptor in the touch neurons of C. elegans steers their axons dorsally. Nature 364: 327–330.
92. Hammarlund, M., and Y. Jin, 2014 Axon regeneration in C. elegans. Curr. Opin. Neurobiol. 27: 199–207.
93. Hammarlund, M., W. S. Davis, and E. M. Jorgensen, 2000 Mutations in beta-spectrin disrupt axon outgrowth and sarcomere structure. J. Cell Biol. 149: 931–942.
94. Hammarlund, M., E. M. Jorgensen, and M. J. Bastiani, 2007 Axons break in animals lacking beta-spectrin. J. Cell Biol. 176: 269–275.
95. Hammarlund, M., P. Nix, L. Hauth, E. M. Jorgensen, and M. Bastiani, 2009 Axon regeneration requires a conserved MAP kinase pathway. Science 323: 802–806.
96. Hao, J. C., T. W. Yu, K. Fujisawa, J. G. Culotti, K. Gengyo-Ando et al., 2001 C. elegans slit acts in midline, dorsal-ventral, and anterior-posterior guidance via the SAX-3/robo receptor. Neuron 32: 25–38.
97. Hao, J. C., C. E. Adler, L. Mebane, F. B. Gertler, C. I. Bargmann et al., 2010 The tripartite motif protein MADD-2 functions with the receptor UNC-40 (DCC) in netrin-mediated axon attraction and branching. Dev. Cell 18: 950–960.
98. He, Z., and Y. Jin, 2016 Intrinsic control of axon regeneration. Neuron 90: 437–451.
99. Hedgecock, E. M., J. G. Culotti, J. N. Thomson, and L. A. Perkins, 1985 Axonal guidance mutants of Caenorhabditis elegans identified by filling sensory neurons with fluorescein dyes. Dev. Biol. 111: 158–170.
100. Hedgecock, E. M., J. G. Culotti, D. H. Hall, and B. D. Stern, 1987 Genetics of cell and axon migrations in Caenorhabditis elegans. Development 100: 365–382.
101. Hedgecock, E. M., J. G. Culotti, and D. H. Hall, 1990 The unc-5, unc-6, and unc-40 genes guide circumferential migrations of pioneer axons and mesodermal cells on the epidermis in C. elegans. Neuron 4: 61–85.
102. Hekimi, S.,and D. Kershaw,1993 Axonalguidancedefectsin a Caenorhabditis elegans mutant reveal cell-extrinsic determinants of neuronal morphology. J. Neurosci. 13: 4254– 4271.
103. Hill, E., I. D. Broadbent, C. Chothia, and J. Pettitt, 2001 Cadherin superfamily proteins in Caenorhabditis elegans and Drosophila melanogaster. J. Mol. Biol. 305: 1011–1024.
104. Hilliard, M. A., and C. I. Bargmann, 2006 Wnt signals and frizzled activity orient anterior-posterior axon outgrowth in C. elegans. Dev. Cell 10: 379–390.
105. Hobert, O., and H. Bülow, 2003 Development and maintenance of neuronal architecture at the ventral midline of C. elegans. Curr. Opin. Neurobiol. 13: 70–78.
106. Honigberg, L., and C. Kenyon, 2000 Establishment of left/right asymmetry in neuroblast migration by UNC-40/DCC, UNC-73/Trio and DPY-19 proteins in C. elegans. Development 127: 4655–4668.
107. Huang, C. C., D. H. Hall, E. M. Hedgecock, G. Kao, V. Karantza et al., 2003 Laminin alpha subunits and their role in C. elegans development. Development 130: 3343–3358.
108. Huang, X., H. J. Cheng, M. Tessier-Lavigne, and Y. Jin, 2002 MAX-1, a novel PH/MyTH4/FERM domain cytoplasmic protein implicated in netrin-mediated axon repulsion. Neuron 34: 563–576.
109. Huang, X., P. Huang, M. K. Robinson, M. J. Stern, and Y. Jin, 2003 UNC-71, a disintegrin and metalloprotease (ADAM) protein, regulates motor axon guidance and sex myoblast migration in C. elegans. Development 130: 3147–3161.
110. Hubert, T., Z. Wu, A. D. Chisholm, and Y. Jin, 2014 S6 kinase inhibits intrinsic axon regeneration capacity via AMP kinase in Caenorhabditis elegans. J. Neurosci. 34: 758–763.
111. Hudson, M. L., T. Kinnunen, H. N. Cinar, and A. D. Chisholm, 2006 C. elegans Kallmann syndrome protein KAL-1 interacts with syndecan and glypican to regulate neuronal cell migrations. Dev. Biol. 294: 352–365.
112. Hutter, H., 2003 Extracellular cues and pioneers act together to guide axons in the ventral cord of C. elegans. Development 130: 5307–5318.
113. Hutter, H., B. E. Vogel, J. D. Plenefisch, C. R. Norris, R. B. Proenca et al., 2000 Conservation and novelty in the evolution of cell adhesion and extracellular matrix genes. Science 287: 989–994.
114. Hutter, H., I. Wacker, C. Schmid, and E. M. Hedgecock, 2005 Novel genes controlling ventral cord asymmetry and navigation of pioneer axons in C. elegans. Dev.Biol.284:260–272.
115. Ishii, N., W. G. Wadsworth, B. D. Stern, J. G. Culotti, and E. M. Hedgecock, 1992 UNC-6, a laminin-related protein, guides cell and pioneer axon migrations in C. elegans. Neuron 9: 873–881.
116. Jarrell, T. A., Y. Wang, A. E. Bloniarz, C. A. Brittin, M. Xu et al., 2012 The connectome of a decision-making neural network. Science 337: 437–444.
117. Johnson, R. P., and J. M. Kramer, 2012 C. elegans dystroglycan coordinates responsiveness of follower axons to dorsal/ventral and anterior/posterior guidance cues. Dev. Neurobiol. 72: 1498–1515.
118. Kaletsky, R., V. Lakhina, R. Arey, A. Williams, J. Landis et al., 2016 The C. elegans adult neuronal IIS/FOXO transcriptome reveals adult phenotype regulators. Nature 529: 92–96.
119. Kang, S. H., and J. M. Kramer, 2000 Nidogen is nonessential and not required for normal type IV collagen localization in Caenorhabditis elegans. Mol. Biol. Cell 11: 3911–3923.
120. Kao, G., C. C. Huang, E. M. Hedgecock, D. H. Hall, and W. G. Wadsworth, 2006 The role of the laminin beta subunit in laminin heterotrimer assembly and basement membrane function and development in C. elegans. Dev. Biol. 290: 211–219.
121. Kasthuri,N.,K.J.Hayworth,D.R.Berger,R.L.Schalek,J.A.Conchello et al., 2015 Saturated reconstruction of a volume of neocortex. Cell 162: 648–661.
122. Katidou, M., N. Tavernarakis, and D. Karagogeos, 2013 The con-tactin RIG-6 mediates neuronal and non-neuronal cell migration in Caenorhabditis elegans. Dev. Biol. 373: 184–195.
123. Kawano, T., H. Zheng, D. C. Merz, Y. Kohara, K. K. Tamai et al., 2009 C. elegans mig-6 encodes papilin isoforms that affect distinct aspects of DTC migration, and interacts genetically with mig-17 and collagen IV. Development 136: 1433–1442.
124. Kawano, Y., T. Yoshimura, D. Tsuboi, S. Kawabata, T. Kaneko-Kawano et al., 2005 CRMP-2 is involved in kinesin-1-dependent transport of the Sra-1/WAVE1 complex and axon formation. Mol. Cell. Biol. 25: 9920–9935.
125. Keino-Masu, K., M. Masu, L. Hinck, E. D. Leonardo, S. S. Chan et al., 1996 Deleted in Colorectal Cancer (DCC) encodes a netrin receptor. Cell 87: 175–185.
126. Kennedy, T. E., T. Serafini, J. R. de la Torre, and M. Tessier-Lavigne, 1994 Netrins are diffusible chemotropic factors for commissural axons in the embryonic spinal cord. Cell 78: 425–435.
127. Kennerdell, J. R., R. D. Fetter, and C. I. Bargmann, 2009 Wnt-Ror signaling to SIA and SIB neurons directs anterior axon guidance and nerve ring placement in C. elegans. Development 136: 3801–3810.
128. Killeen, M. T., and S. S. Sybingco, 2008 Netrin, Slit and Wnt receptors allow axons to choose the axis of migration. Dev. Biol. 323: 143–151.
129. Kim, S., and W. G. Wadsworth, 2000 Positioning of longitudinal nerves in C. elegans by nidogen. Science 288: 150–154.
130. Kim, S., X. C. Ren, E. Fox, and W. G. Wadsworth, 1999 SDQR migrations in Caenorhabditis elegans are controlled by multiple guidance cues and changing responses to netrin UNC-6. Development 126: 3881–3890.
131. Kirszenblat, L., D. Pattabiraman, and M. A. Hilliard, 2011 LIN-44/Wnt directs dendrite outgrowth through LIN-17/Frizzled in C. elegans Neurons. PLoS Biol. 9: e1001157.
132. Kirszenblat, L., B. Neumann, S. Coakley, and M. A. Hilliard, 2013 A dominant mutation in mec-7/beta-tubulin affects axon development and regeneration in Caenorhabditis elegans neurons. Mol. Biol. Cell 24: 285–296.
133. Knobel, K. M., E. M. Jorgensen, and M. J. Bastiani, 1999 Growth cones stall and collapse during axon outgrowth in Caenorhabditis elegans. Development 126: 4489–4498.
134. Kolodkin, A. L., 1998 Semaphorin-mediated neuronal growth cone guidance. Prog. Brain Res. 117: 115–132.
135. Kolodkin, A. L., and M. Tessier-Lavigne, 2011 Mechanisms and molecules of neuronal wiring: a primer. Cold Spring Harb. Perspect. Biol. 3: pii: a001727.
136. Kosmaczewski, S. G., S. M. Han, B. Han, B. Irving Meyer, H. S. Baig et al., 2015 RNA ligation in neurons by RtcB inhibits axon regeneration. Proc. Natl. Acad. Sci. USA 112: 8451–8456.
137. Kramer, J. M., 2005 Basement membranes (September 1, 2005), WormBook, ed. The C. elegans Research Community, WormBook, doi/10.1895/wormbook.1.16.1, http://www.wormbook.org.
138. Krause,M.,J.D.Leslie,M.Stewart,E.M.Lafuente,F.Valderrama et al., 2004 Lamellipodin, an ena/VASP ligand, is implicated in the regulation of lamellipodial dynamics. Dev. Cell 7: 571–583.
139. Kubota, Y., R. Kuroki, and K. Nishiwaki, 2004 A fibulin-1 homolog interacts with an ADAM protease that controls cell migration in C. elegans. Curr. Biol. 14: 2011–2018.
140. Kulkarni, G., H. Li, and W. G. Wadsworth, 2008 CLEC-38, a transmembrane protein with C-type lectin-like domains, negatively regulates UNC-40-mediated axon outgrowth and promotes presynaptic development in Caenorhabditis elegans. J. Neurosci. 28: 4541–4550.
141. Kulkarni, G., Z. Xu, A. M. Mohamed, H. Li, X. Tang et al., 2013 Experimental evidence for UNC-6 (netrin) axon guidance by stochastic fluctuations of intracellular UNC-40 (DCC) outgrowth activity. Biol. Open 2: 1300–1312.
142. Kurup, N., D. Yan, A. Goncharov, and Y. Jin, 2015 Dynamic microtubules drive circuit rewiring in the absence of neurite remodeling. Curr. Biol. 25: 1594–1605.
143. Lai, T., and G. Garriga, 2004 The conserved kinase UNC-51 acts with VAB-8 and UNC-14 to regulate axon outgrowth in C. elegans. Development 131: 5991–6000.
144. Lee, M., E. J. Cram, B. Shen, and J. E. Schwarzbauer, 2001 Roles for beta(pat-3) integrins in development and function of Caenorhabditis elegans muscles and gonads. J. Biol. Chem. 276: 36404–36410.
145. Lemke, G., and M. Reber, 2005 Retinotectal mapping: new insights from molecular genetics. Annu. Rev. Cell Dev. Biol. 21: 551–580.
146. Leonardo, E. D., L. Hinck, M. Masu, K. Keino-Masu, S. L. Ackerman et al., 1997 Vertebrate homologues of C. elegans UNC-5 are candidate netrin receptors. Nature 386: 833–838.
147. Leung-Hagesteijn, C., A. M. Spence, B. D. Stern, Y. Zhou, M. W. Su et al., 1992 UNC-5, a transmembrane protein with immunoglobulin and thrombospondin type 1 domains, guides cell and pioneer axon migrations in C. elegans. Cell 71: 289–299.
148. Levy-Strumpf, N., 2016 Orchestrating A/P and D/V guidance - A Wnt/netrin tale. Worm 5: e1146857.
149. Levy-Strumpf, N., and J. G. Culotti, 2007 VAB-8, UNC-73 and MIG-2 regulate axon polarity and cell migration functions of UNC-40 in C. elegans. Nat. Neurosci. 10: 161–168.
150. Levy-Strumpf, N., and J. G. Culotti, 2014 Netrins and Wnts function redundantly to regulate antero-posterior and dorso-ventral guidance in C. elegans. PLoS Genet. 10: e1004381.
151. Levy-Strumpf, N., M. Krizus, H. Zheng, L. Brown, and J. G. Culotti, 2015 The Wnt frizzled receptor MOM-5 regulates the UNC-5 netrin receptor through small GTPase-dependent signaling to determine the polarity of migrating Cells. PLoS Genet. 11: e1005446.
152. Li, C., N. Hisamoto, P. Nix, S. Kanao, T. Mizuno et al., 2012 The growth factor SVH-1 regulates axon regeneration in C. elegans via the JNK MAPK cascade. Nat. Neurosci. 15: 551–557.
153. Li, C., N. Hisamoto, and K. Matsumoto, 2015 Axon regeneration is regulated by Ets-C/EBP transcription complexes generated by activation of the cAMP/Ca2+ signaling pathways. PLoS Genet. 11: e1005603.
154. Li, H., G. Kulkarni, and W. G. Wadsworth, 2008 RPM-1, a Caenorhabditis elegans protein that functions in presynaptic differentiation, negatively regulates axon outgrowth by controlling SAX-3/robo and UNC-5/UNC5 activity. J. Neurosci. 28: 3595–3603.
155. Loria, P. M., A. Duke, J. B. Rand, and O. Hobert, 2003 Two neuronal, nuclear-localized RNA binding proteins involved in synaptic transmission. Curr. Biol. 13: 1317–1323.
156. Lucanic, M., M. Kiley, N. Ashcroft, N. L’Etoile, and H. J. Cheng, 2006 The Caenorhabditis elegans P21-activated kinases are dif-ferentially required for UNC-6/netrin-mediated commissural motor axon guidance. Development 133: 4549–4559.
157. Lundquist, E. A., R. K. Herman, J. E. Shaw, and C. I. Bargmann, 1998 UNC-115, a conserved protein with predicted LIM and actin-binding domains, mediates axon guidance in C. elegans. Neuron 21: 385–392.
158. Lundquist, E. A., P. W. Reddien, E. Hartwieg, H. R. Horvitz, and C. I. Bargmann, 2001 Three C. elegans Rac proteins and several alternative Rac regulators control axon guidance, cell migration and apoptotic cell phagocytosis. Development 128: 4475–4488.
159. MacNeil, L. T., W. R. Hardy, T. Pawson, J. L. Wrana, and J. G. Culotti, 2009 UNC-129 regulates the balance between UNC-40 dependent and independent UNC-5 signaling pathways. Nat. Neurosci. 12: 150–155.
160. Maniar, T. A., M. Kaplan, G. J. Wang, K. Shen, L. Wei et al., 2012 UNC-33 (CRMP) and ankyrin organize microtubules and localize kinesin to polarize axon-dendrite sorting. Nat. Neurosci. 15: 48–56.
161. Marcette, J. D., J. J. Chen, and M. L. Nonet, 2014 The Caenorhabditis elegans microtubule minus-end binding homolog PTRN-1 stabilizes synapses and neurites. eLife 3: e01637.
162. Maro, G. S., M. P. Klassen, and K. Shen, 2009 A beta-catenin-dependent Wnt pathway mediates anteroposterior axon guidance in C. elegans motor neurons. PLoS One 4: e4690.
163. McIntire, S. L., G. Garriga, J. White, D. Jacobson, and H. R. Horvitz, 1992 Genes necessary for directed axonal elongation or fasciculation in C. elegans. Neuron 8: 307–322.
164. McShea, M. A., K. L. Schmidt, M. L. Dubuke, C. E. Baldiga, M. E. Sullender et al., 2013 Abelson interactor-1 (ABI-1) interacts with MRL adaptor protein MIG-10 and is required in guided cell migrations and process outgrowth in C. elegans. Dev. Biol. 373: 1–13.
165. Mehlen, P., C. Delloye-Bourgeois, and A. Chédotal, 2011 Novel roles for Slits and netrins: axon guidance cues as anticancer targets? Nat. Rev. Cancer 11: 188–197.
166. Meighan, C. M., and J. E. Schwarzbauer, 2007 Control of C. elegans hermaphrodite gonad size and shape by vab-3/Pax6-mediated regulation of integrin receptors. Genes Dev. 21: 1615–1620.
167. Meng, L., C. H. Chen, and D. Yan, 2016 Regulation of gap junction dynamics by UNC-44/ankyrin and UNC-33/CRMP through VAB-8 in C. elegans neurons. PLoS Genet. 12: e1005948.
168. Merz, D. C., H. Zheng, M. T. Killeen, A. Krizus, and J. G. Culotti, 2001 Multiple signaling mechanisms of the unc-6/netrin receptors unc-5 and unc-40/dcc in vivo. Genetics 158: 1071– 1080.
169. Merz, D. C., G. Alves, T. Kawano, H. Zheng, and J. G. Culotti, 2003 UNC-52/perlecan affects gonadal leader cell migrations in C. elegans hermaphrodites through alterations in growth factor signaling. Dev. Biol. 256: 173–186.
170. Mizuno, T., N. Hisamoto, T. Terada, T. Kondo, M. Adachi et al., 2004 The Caenorhabditis elegans MAPK phosphatase VHP-1 mediates a novel JNK-like signaling pathway in stress response. EMBO J. 23: 2226–2234.
171. Moffat, L. L., R. E. Robinson, A. Bakoulis, and S. G. Clark, 2014 The conserved transmembrane RING finger protein PLR-1 downregu-lates Wnt signaling by reducing Frizzled, Ror and Ryk cell-surface levels in C. elegans. Development 141: 617–628.
172. Mohamed, A. M., and I. D. Chin-Sang, 2006 Characterization of loss-of-function and gain-of-function Eph receptor tyrosine kinase signaling in C. elegans axon targeting and cell migration. Dev. Biol. 290: 164–176.
173. Mohamed, A. M., J. R. Boudreau, F. P. Yu, J. Liu, and I. D. Chin-Sang, 2012 The Caenorhabditis elegans Eph receptor activates NCK and N-WASP, and inhibits Ena/VASP to regulate growth cone dynamics during axon guidance. PLoS Genet. 8: e1002513.
174. Mohler, W. A., G. Shemer, J. J. del Campo, C. Valansi, E. Opoku-Serebuoh et al., 2002 The type I membrane protein EFF-1 is essential for developmental cell fusion. Dev. Cell 2: 355–362.
175. Morrissey, M. A., R. Jayadev, G. R. Miley, C. A. Blebea, Q. Chi et al., 2016 SPARC promotes cell invasion in vivo by decreasing type IV collagen levels in the basement membrane. PLoS Genet. 12: e1005905.
176. Murshed, M., N. Smyth, N. Miosge, J. Karolat, T. Krieg et al., 2000 The absence of nidogen 1 does not affect murine basement membrane formation. Mol. Cell. Biol. 20: 7007–7012.
177. Nakamura, F., K. Kumeta, T. Hida, T. Isono, Y. Nakayama et al., 2014 Amino- and carboxyl-terminal domains of Filamin-A interact with CRMP1 to mediate Sema3A signalling. Nat. Commun. 5: 5325.
178. Nakata, K., B. Abrams, B. Grill, A. Goncharov, X. Huang et al., 2005 Regulation of a DLK-1 and p38 MAP kinase pathway by the ubiquitin ligase RPM-1 is required for presynaptic development. Cell 120: 407–420.
179. Nash, B., A. Colavita, H. Zheng, P. J. Roy, and J. G. Culotti, 2000 The forkhead transcription factor UNC-130 is required for the graded spatial expression of the UNC-129 TGF-beta guidance factor in C. elegans. Genes Dev. 14: 2486–2500.
180. Nelson, J. C., and D. A. Colón-Ramos, 2013 Serotonergic neuro-secretory synapse targeting is controlled by netrin-releasing guidepost neurons in Caenorhabditis elegans. J. Neurosci. 33: 1366–1376.
181. Neumann, S., and C. J. Woolf, 1999 Regeneration of dorsal column fibers into and beyond the lesion site following adult spinal cord injury. Neuron 23: 83–91.
182. Neumann, B., K. C. Nguyen, D. H. Hall, A. Ben-Yakar, and M. A. Hilliard, 2011 Axonal regeneration proceeds through specific axonal fusion in transected C. elegans neurons. Dev. Dyn. 240: 1365–1372.
183. Neumann, B., S. Coakley, R. Giordano-Santini, C. Linton, E. S. Lee et al., 2015 EFF-1-mediated regenerative axonal fusion requires components of the apoptotic pathway. Nature 517: 219–222.
184. Nichols, A. L., E. Meelkop, C. Linton, R. Giordano-Santini, R. K. Sullivan et al., 2016 The apoptotic engulfment machinery regulates axonal degeneration in C. elegans neurons. Cell Reports 14: 1673–1683.
185. Nishiwaki, K., N. Hisamoto, and K. Matsumoto, 2000 A metalloprotease disintegrin that controls cell migration in Caenorhabditis elegans. Science 288: 2205–2208.
186. Nix, P., N. Hisamoto, K. Matsumoto, and M. Bastiani, 2011 Axon regeneration requires coordinate activation of p38 and JNK MAPK pathways. Proc. Natl. Acad. Sci. USA 108: 10738–10743.
187. Nix, P., M. Hammarlund, L. Hauth, M. Lachnit, E. M. Jorgensen et al., 2014 Axon regeneration genes identified by RNAi screening in C. elegans. J. Neurosci. 34: 629–645.
188. Norris, A. D., and E. A. Lundquist, 2011 UNC-6/netrin and its receptors UNC-5 and UNC-40/DCC modulate growth cone protrusion in vivo in C. elegans. Development 138: 4433–4442.
189. Norris, A. D., J. O. Dyer, and E. A. Lundquist, 2009 The Arp2/3 complex, UNC-115/abLIM, and UNC-34/enabled regulate axon guidance and growth cone filopodia formation in Caenorhabditis elegans. Neural Dev. 4: 38.
190. Norris, A. D., L. Sundararajan, D. E. Morgan, Z. J. Roberts, and E. A. Lundquist, 2014 The UNC-6/netrin receptors UNC-40/DCC and UNC-5 inhibit growth cone filopodial protrusion via UNC-73/Trio, Rac-like GTPases and UNC-33/CRMP. Development 141: 4395–4405.
191. O’Rourke, S. M., S. N. Christensen, and B. Bowerman, 2010 Caenorhabditis elegans EFA-6 limits microtubule growth at the cell cortex. Nat. Cell Biol. 12: 1235–1241.
192. Onishi, K., E. Hollis, and Y. Zou, 2014 Axon guidance and injury-lessons from Wnts and Wnt signaling. Curr. Opin. Neurobiol. 27: 232–240.
193. Opperman, K. J., and B. Grill, 2014 RPM-1 is localized to distinct subcellular compartments and regulates axon length in GABAergic motor neurons. Neural Dev. 9: 10.
194. Oren-Suissa M., D.H. Hall, M. Treinin, G. Shemer, and B. Podbilewicz, 2010 The fusogen EFF-1 controls sculpting of mechanosensory dendrites. Science 328: 1285–1288.
195. Otsuka, A. J., R. Franco, B. Yang, K. H. Shim, L. Z. Tang et al., 1995 An ankyrin-related gene (unc-44) is necessary for proper axonal guidance in Caenorhabditis elegans. J. Cell Biol. 129: 1081–1092.
196. Pan, C. L., J. E. Howell, S. G. Clark, M. Hilliard, S. Cordes et al., 2006 Multiple Wnts and frizzled receptors regulate anteriorly directed cell and growth cone migrations in Caenorhabditis elegans. Dev. Cell 10: 367–377.
197. Park, J., P. L. Knezevich, W. Wung, S. N. O’Hanlon, A. Goyal et al., 2011 A conserved juxtacrine signal regulates synaptic partner recognition in Caenorhabditis elegans. Neural Dev. 6: 28.
198. Pastuhov, S. I., K. Fujiki, P. Nix, S. Kanao, M. Bastiani et al., 2012 Endocannabinoid-Goalpha signalling inhibits axon regeneration in Caenorhabditis elegans by antagonizing Gqal-pha-PKC-JNK signalling. Nat. Commun. 3: 1136.
199. Pastuhov, S. I., N. Hisamoto, and K. Matsumoto, 2015 MAP kinase cascades regulating axon regeneration in C. elegans. Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. 91: 63–75.
200. Pastuhov, S.I., K. Matsumoto, and N. Hisamoto, 2016 Endocannabinoid signaling regulates regenerative axon navigation in Caenorhabditis elegans via the GPCRs NPR-19 and NPR-32. Genes Cells 21: 696–705.
201. Patel, M. R., E. K. Lehrman, V. Y. Poon, J. G. Crump, M. Zhen et al., 2006 Hierarchical assembly of presynaptic components in defined C. elegans synapses. Nat. Neurosci. 9: 1488–1498.
202. Peckol, E. L., J. A. Zallen, J. C. Yarrow, and C. I. Bargmann, 1999 Sensory activity affects sensory axon development in C. elegans. Development 126: 1891–1902.
203. Perkins, L. A., E. M. Hedgecock, J. N. Thomson, and J. G. Culotti, 1986 Mutant sensory cilia in the nematode Caenorhabditis elegans. Dev. Biol. 117: 456–487.
204. Pilon, M., 2014 Developmental genetics of the Caenorhabditis elegans pharynx. Wiley Interdiscip. Rev. Dev. Biol. 3: 263–280.
205. Pinan-Lucarre, B., C. V. Gabel, C. P. Reina, S. E. Hulme, S. S. Shevkoplyas et al., 2012 The core apoptotic executioner proteins CED-3 and CED-4 promote initiation of neuronal regeneration in Caenorhabditis elegans. PLoS Biol. 10: e1001331.
206. Pocock, R., and O. Hobert, 2008 Oxygen levels affect axon guidance and neuronal migration in Caenorhabditis elegans. Nat. Neurosci. 11: 894–900.
207. Poinat, P., A. De Arcangelis, S. Sookhareea, X. Zhu, E. M. Hedgecock et al., 2002 A conserved interaction between beta1 integrin/ PAT-3 and Nck-interacting kinase/MIG-15 that mediates commissural axon navigation in C. elegans. Curr. Biol. 12: 622–631.
208. Pollard, T. D., and G. G. Borisy, 2003 Cellular motility driven by assembly and disassembly of actin filaments. Cell 112: 453–465.
209. Pollard, T. D., and J. A. Cooper, 2009 Actin, a central player in cell shape and movement. Science 326: 1208–1212.
210. Polleux, F., and W. Snider, 2010 Initiating and growing an axon. Cold Spring Harb. Perspect. Biol. 2: a001925.
211. Poon, V. Y., M. P. Klassen, and K. Shen, 2008 UNC-6/netrin and its receptor UNC-5 locally exclude presynaptic components from dendrites. Nature 455: 669–673.
212. Poulain, F. E., and H. J. Yost, 2015 Heparan sulfate proteoglycans: a sugar code for vertebrate development? Development 142: 3456–3467.
213. Prasad, B. C., and S. G. Clark, 2006 Wnt signaling establishes anteroposterior neuronal polarity and requires retromer in C. elegans. Development 133: 1757–1766.
214. Prasad, B. C., B. Ye, R. Zackhary, K. Schrader, G. Seydoux et al., 1998 unc-3, a gene required for axonal guidance in Caenorhabditis elegans, encodes a member of the O/E family of transcription factors. Development 125: 1561–1568.
215. Quinn, C. C., and W. G. Wadsworth, 2008 Axon guidance: asymmetric signaling orients polarized outgrowth. Trends Cell Biol. 18: 597–603.
216. Quinn, C. C., D. S. Pfeil, E. Chen, E. L. Stovall, M. V. Harden et al., 2006 UNC-6/netrin and SLT-1/slit guidance cues orient axon outgrowth mediated by MIG-10/RIAM/lamellipodin. Curr. Biol. 16: 845–853.
217. Quinn, C. C., D. S. Pfeil, and W. G. Wadsworth, 2008 CED-10/Rac1 mediates axon guidance by regulating the asymmetric distribution of MIG-10/lamellipodin. Curr. Biol. 18: 808–813.
218. Ren, X. C., S. Kim, E. Fox, E. M. Hedgecock, and W. G. Wadsworth, 1999 Role of netrin UNC-6 in patterning the longitudinal nerves of Caenorhabditis elegans. J. Neurobiol. 39: 107–118.
219. Rhiner, C., S. Gysi, E. Frohli, M. O. Hengartner, and A. Hajnal, 2005 Syndecan regulates cell migration and axon guidance in C. elegans. Development 132: 4621–4633.
220. Richardson,C.E.,K.A.Spilker,J.G.Cueva,J.Perrino,M.B.Goodman et al., 2014 PTRN-1, a microtubule minus end-binding CAMSAP homolog, promotes microtubule function in Caenorhabditis elegans neurons. eLife 3: e01498.
221. Rogalski, T. M., B. D. Williams, G. P. Mullen, and D. G. Moerman, 1993 Products of the unc-52 gene in Caenorhabditis elegans are homologous to the core protein of the mammalian basement membrane heparan sulfate proteoglycan. Genes Dev. 7: 1471– 1484.
222. Rohde, C. B., and M. F. Yanik, 2011 Subcellular in vivo time-lapse imaging and optical manipulation of Caenorhabditis elegans in standard multiwell plates. Nat. Commun. 2: 271.
223. Roy, P. J., H. Zheng, C. E. Warren, and J. G. Culotti, 2000 mab-20 encodes Semaphorin-2a and is required to prevent ectopic cell contacts during epidermal morphogenesis in Caenorhabditis elegans. Development 127: 755–767.
224. Salzberg, Y., C. A. Díaz-Balzac, N. J. Ramirez-Suarez, M. Attreed, E. Tecle et al., 2013 Skin-derived cues control arborization of sensory dendrites in Caenorhabditis elegans. Cell155:308– 320.
225. Samara, C., C. B. Rohde, C. L. Gilleland, S. Norton, S. J. Haggarty et al., 2010 Large-scale in vivo femtosecond laser neurosurgery screen reveals small-molecule enhancer of regeneration. Proc. Natl. Acad. Sci. USA 107: 18342–18347.
226. Sasakura, H., H. Inada, A. Kuhara, E. Fusaoka, D. Takemoto et al., 2005 Maintenance of neuronal positions in organized ganglia by SAX-7, a Caenorhabditis elegans homologue of L1. EMBO J. 24: 1477–1488.
227. Sawa, H., and H. C. Korswagen, 2013 Wnt signaling in C. elegans (December 9, 2013), WormBook, ed. The C. elegans Research Community, WormBook, doi/10.1895/wormbook.1.7.2, http:// www.wormbook.org.
228. Schaefer, A. M., G. D. Hadwiger, and M. L. Nonet, 2000 rpm-1, a conserved neuronal gene that regulates targeting and synaptogenesis in C. elegans. Neuron 26: 345–356.
229. Schmidt, K. L., N. Marcus-Gueret, A. Adeleye, J. Webber, D. Baillie et al., 2009 The cell migration molecule UNC-53/NAV2 is linked to the ARP2/3 complex by ABI-1. Development 136: 563–574.
230. Schmitz, C., P. Kinge, and H. Hutter, 2007 Axon guidance genes identified in a large-scale RNAi screen using the RNAi-hypersensitive Caenorhabditis elegans strain nre-1(hd20) lin-15b(hd126). Proc. Natl. Acad. Sci. USA 104: 834–839.
231. Schwarz, V., J. Pan, S. Voltmer-Irsch, and H. Hutter, 2009 IgCAMs redundantly control axon navigation in Caenorhabditis elegans. Neural Dev. 4: 13.
232. Schwieterman, A. A., A. N. Steves, V. Yee, C. J. Donelson, M. R. Bentley et al., 2016 The Caenorhabditis elegans ephrin EFN-4 functions non-cell autonomously with heparan sulfate proteoglycans to promote axon outgrowth and branching. Genetics 202: 639–660.
233. Schymeinsky, J., S. Nedbal, N. Miosge, E. Pöschl, C. Rao et al., 2002 Gene structure and functional analysis of the mouse nidogen-2 gene: nidogen-2 is not essential for basement membrane formation in mice. Mol. Cell. Biol. 22: 6820–6830.
234. Seetharaman, A., G. Selman, R. Puckrin, L. Barbier, E. Wong et al., 2011 MADD-4 is a secreted cue required for midline-oriented guidance in Caenorhabditis elegans. Dev. Cell 21: 669–680.
235. Serafini, T., T. E. Kennedy, M. J. Galko, C. Mirzayan, T. M. Jessell et al., 1994 The netrins define a family of axon outgrowth-promoting proteins homologous to C. elegans UNC-6. Cell 78: 409–424.
236. Shaham, S., 2015 Glial development and function in the nervous system of Caenorhabditis elegans. Cold Spring Harb. Perspect. Biol. 7: a020578.
237. Shakir, M. A., J. S. Gill, and E. A. Lundquist, 2006 Interactions of UNC-34 Enabled with Rac GTPases and the NIK kinase MIG-15 in Caenorhabditis elegans axon pathfinding and neuronal migration. Genetics 172: 893–913.
238. Shakir, M. A., K. Jiang, E. C. Struckhoff, R. S. Demarco, F. B. Patel et al., 2008 The Arp2/3 activators WAVE and WASP have distinct genetic interactions with Rac GTPases in Caenorhabditis elegans axon guidance. Genetics 179: 1957–1971.
239. Shaye, D. D., and I. Greenwald, 2011 OrthoList: a compendium of C. elegans genes with human orthologs. PLoS One 6: e20085.
240. Sherwood, D. R., and P. W. Sternberg, 2003 Anchor cell invasion into the vulval epithelium in C. elegans. Dev. Cell 5: 21–31.
241. Siddiqui, S. S., and J. G. Culotti, 1991 Examination of neurons in wild type and mutants of Caenorhabditis elegans using antibodies to horseradish peroxidase. J. Neurogenet. 7: 193– 211.
242. Siddiqui, S. S., E. Aamodt, F. Rastinejad, and J. Culotti, 1989 Anti-tubulin monoclonal antibodies that bind to specific neurons in Caenorhabditis elegans. J. Neurosci. 9: 2963–2972.
243. Song, S., B. Zhang, H. Sun, X. Li, Y. Xiang et al., 2010 A Wnt-Frz/Ror-Dsh pathway regulates neurite outgrowth in Caenorhabditis elegans. PLoS Genet. 6: e1001056.
244. Song, Y., D. Sretavan, E. A. Salegio, J. Berg, X. Huang et al., 2015 Regulation of axon regeneration by the RNA repair and splicing pathway. Nat. Neurosci. 18: 817–825.
245. Soto, M. C., H. Qadota, K. Kasuya, M. Inoue, D. Tsuboi et al., 2002 The GEX-2 and GEX-3 proteins are required for tissue morphogenesis and cell migrations in C. elegans. Genes Dev. 16: 620–632.
246. Stavoe, A. K., and D. A. Colón-Ramos, 2012 Netrin instructs synaptic vesicle clustering through Rac GTPase, MIG-10, and the actin cytoskeleton. J. Cell Biol. 197: 75–88.
247. Stavoe, A. K., J. C. Nelson, L. A. Martínez-Velázquez, M. Klein, A. D. Samuel et al., 2012 Synaptic vesicle clustering requires a distinct MIG-10/Lamellipodin isoform and ABI-1 downstream from Netrin. Genes Dev. 26: 2206–2221.
248. Steimel, A., L. Wong, E. H. Najarro, B. D. Ackley, G. Garriga et al., 2010 The Flamingo ortholog FMI-1 controls pioneer-dependent navigation of follower axons in C. elegans. Development 137: 3663–3673.
249. Stringham, E. G., and K. L. Schmidt, 2009 Navigating the cell: UNC-53 and the navigators, a family of cytoskeletal regulators with multiple roles in cell migration, outgrowth and trafficking. Cell Adhes. Migr. 3: 342–346.
250. Struckhoff, E. C., and E. A. Lundquist, 2003 The actin-binding protein UNC-115 is an effector of Rac signaling during axon pathfinding in C. elegans. Development 130: 693–704.
251. Sun, L., J. Shay, M. McLoed, K. Roodhouse, S. H. Chung et al., 2014 Neuronal regeneration in C. elegans requires subcellular calcium release by ryanodine receptor channels and can be enhanced by optogenetic stimulation. J. Neurosci. 34: 15947–15956.
252. Takenawa, T., and S. Suetsugu, 2007 The WASP-WAVE protein network: connecting the membrane to the cytoskeleton. Nat. Rev. Mol. Cell Biol. 8: 37–48.
253. Tamai, K. K., and K. Nishiwaki, 2007 bHLH transcription factors regulate organ morphogenesis via activation of an ADAMTS protease in C. elegans. Dev. Biol. 308: 562–571.
254. Tang, N. H., and A. D. Chisholm, 2016 Regulation of microtubule dynamics in axon regeneration: insights from C. elegans. F1000Res 5. pii: F1000.
255. Tang, X., and W. G. Wadsworth, 2014 SAX-3 (Robo) and UNC-40 (DCC) regulate a directional bias for axon guidance in response to multiple extracellular cues. PLoS One 9: e110031.
256. Tank, E. M., K. E. Rodgers, and C. Kenyon, 2011 Spontaneous age-related neurite branching in Caenorhabditis elegans. J. Neurosci. 31: 9279–9288.
257. Tedeschi, A., 2011 Tuning the orchestra: transcriptional pathways controlling axon regeneration. Front. Mol. Neurosci. 4: 60.
258. Tessier-Lavigne, M., and C. S. Goodman, 1996 The molecular biology of axon guidance. Science 274: 1123–1133.
259. Teulière, J., C. Gally, G. Garriga, M. Labouesse, and E. Georges-Labouesse, 2011 MIG-15 and ERM-1 promote growth cone directional migration in parallel to UNC-116 and WVE-1. Development 138: 4475–4485.
260. Tian, D., M. Diao, Y. Jiang, L. Sun, Y. Zhang et al., 2015 Anillin regulates neuronal migration and neurite growth by linking RhoG to the actin cytoskeleton. Curr. Biol. 25: 1135–1145.
261. Torpe, N., and R. Pocock, 2014 Regulation of axonal midline guidance by prolyl 4-hydroxylation in Caenorhabditis elegans. J. Neurosci. 34: 16348–16357.
262. Toth, M. L., I. Melentijevic, L. Shah, A. Bhatia, K. Lu et al., 2012 Neurite sprouting and synapse deterioration in the aging Caenorhabditis elegans nervous system. J. Neurosci. 32: 8778–8790.
263. Tu, H., B. Pinan-Lucarré, T. Ji, M. Jospin, and J. L. Bessereau, 2015 C. elegans punctin clusters GABA(A) receptors via neuroligin binding and UNC-40/DCC recruitment. Neuron 86: 1407–1419.
264. Tucker, M., and M. Han, 2008 Muscle cell migrations of C. elegans are mediated by the alpha-integrin INA-1, Eph receptor VAB-1, and a novel peptidase homologue MNP-1. Dev. Biol. 318: 215–223.
265. Tulgren, E. D., S. M. Turgeon, K. J. Opperman, and B. Grill, 2014 The nesprin family member ANC-1 regulates synapse formation and axon termination by functioning in a pathway with RPM-1 and b-Catenin. PLoS Genet. 10: e1004481.
266. Unsoeld, T., J. O. Park, and H. Hutter, 2013 Discoidin domain receptors guide axons along longitudinal tracts in C. elegans. Dev. Biol. 374: 142–152.
267. Viveiros, R., H. Hutter, and D. G. Moerman, 2011 Membrane extensions are associated with proper anterior migration of muscle cells during Caenorhabditis elegans embryogenesis. Dev. Biol. 358: 189–200.
268. Wacker, I., V. Schwarz, E. M. Hedgecock, and H. Hutter, 2003 zag-1, a Zn-finger homeodomain transcription factor controlling neuronal differentiation and axon outgrowth in C. elegans. Development 130: 3795–3805.
269. Wadsworth, W. G., 2002 Moving around in a worm: netrin UNC-6 and circumferential axon guidance in C. elegans. Trends Neurosci. 25: 423–429.
270. Wadsworth, W. G., and E. M. Hedgecock, 1996 Hierarchical guidance cues in the developing nervous system of C. elegans. Bio-Essays 18: 355–362.
271. Wadsworth, W. G., H. Bhatt, and E. M. Hedgecock, 1996 Neuroglia and pioneer neurons express UNC-6 to provide global and local netrin cues for guiding migrations in C. elegans. Neuron 16: 35–46.
272. Wang, F., 2009 The signaling mechanisms underlying cell polarity and chemotaxis. Cold Spring Harb. Perspect. Biol. 1: a002980.
273. Wang, X., P. J. Roy, S. J. Holland, L. W. Zhang, J. G. Culotti et al., 1999 Multiple ephrins control cell organization in C. elegans using kinase-dependent and -independent functions of the VAB-1 Eph receptor. Mol. Cell 4: 903–913.
274. Wang, X., J. Kweon, S. Larson, and L. Chen, 2005 A role for the C. elegans L1CAM homologue lad-1/sax-7 in maintaining tissue attachment. Dev. Biol. 284: 273–291.
275. Wang, X., W. Zhang, T. Cheever, V. Schwarz, K. Opperman et al., 2008 The C. elegans L1CAM homologue LAD-2 functions as a coreceptor in MAB-20/Sema2 mediated axon guidance. J. Cell Biol. 180: 233–246.
276. Wang, Z., Y. Hou, X. Guo, M. van der Voet, M. Boxem et al., 2013 The EBAX-type Cullin-RING E3 ligase and Hsp90 guard the protein quality of the SAX-3/Robo receptor in developing neurons. Neuron 79: 903–916.
277. Wang, Z., L. M. Linden, K. M. Naegeli, J. W. Ziel, Q. Chi et al., 2014 UNC-6 (netrin) stabilizes oscillatory clustering of the UNC-40 (DCC) receptor to orient polarity. J. Cell Biol. 206: 619–633.
278. Ward, S., N. Thomson, J. G. White, and S. Brenner, 1975 Electron microscopical reconstruction of the anterior sensory anatomy of the nematode Caenorhabditis elegans. J. Comp. Neurol. 160: 313–337.
279. Ware, R. W., D. Clark, K. Crossland, and R. L. Russell, 1975 The nerve ring of the nematode Caenorhabditis elegans: sensory input and motor output. J. Comp. Neurol. 162: 71–110.
280. Watari-Goshima, N., K. Ogura, F. W. Wolf, Y. Goshima, and G. Garriga, 2007 C. elegans VAB-8 and UNC-73 regulate the SAX-3 receptor to direct cell and growth-cone migrations. Nat. Neurosci. 10: 169–176.
281. Watkins, T. A., B. Wang, S. Huntwork-Rodriguez, J. Yang, Z. Jiang et al., 2013 DLK initiates a transcriptional program that couples apoptotic and regenerative responses to axonal injury. Proc. Natl. Acad. Sci. USA 110: 4039–4044.
282. White, J. G., 1985 Neuronal connectivity in Caenorhabditis elegans. Trends Neurosci. 8: 277–283.
283. White, J., E. Southgate, J. Thompson, and S. Brenner, 1986 The structure of the nervous system of the nematode Caenorhabditis elegans. Philos. Trans. R. Soc. Lond. B Biol. Sci. 314: 1–340.
284. Wightman, B., R. Baran, and G. Garriga, 1997 Genes that guide growth cones along the C. elegans ventral nerve cord. Development 124: 2571–2580.
285. Williams, B. D., and R. H. Waterston, 1994 Genes critical for muscle development and function in Caenorhabditis elegans identified through lethal mutations. J. Cell Biol. 124: 475–490.
286. Williams, W., P. Nix, and M. Bastiani, 2011 Constructing a low-budget laser axotomy system to study axon regeneration in C. elegans. J. Vis. Exp. 57: 3331.
287. Wu, Z., A. Ghosh-Roy, M. F. Yanik, J. Z. Zhang, Y. Jin et al., 2007 Caenorhabditis elegans neuronal regeneration is influenced by life stage, ephrin signaling, and synaptic branching. Proc. Natl. Acad. Sci. USA 104: 15132–15137.
288. Xu, Y., H. Taru, Y. Jin, and C. C. Quinn, 2015 SYD-1C, UNC-40 (DCC) and SAX-3 (Robo) function interdependently to promote axon guidance by regulating the MIG-2 GTPase. PLoS Genet. 11: e1005185.
289. Xu, Z., H. Li, and W. G. Wadsworth, 2009 The roles of multiple UNC-40 (DCC) receptor-mediated signals in determining neuronal asymmetry induced by the UNC-6 (netrin) ligand. Genetics 183: 941–949.
290. Yam, P. T., and F. Charron, 2013 Signaling mechanisms of non-conventional axon guidance cues: the Shh, BMP and Wnt mor-phogens. Curr. Opin. Neurobiol. 23: 965–973.
291. Yan, D., and Y. Jin, 2012 Regulation of DLK-1 kinase activity by calcium-mediated dissociation from an inhibitory isoform. Neuron 76: 534–548.
292. Yan, D., Z. Wu, A. D. Chisholm, and Y. Jin, 2009 The DLK-1 kinase promotes mRNA stability and local translation in C. elegans synapses and axon regeneration. Cell 138: 1005–1018.
293. Yang, Y., W. S. Lee, X. Tang, and W. G. Wadsworth, 2014 Extracellular matrix regulates UNC-6 (Netrin) axon guidance by controlling the direction of intracellular UNC-40 (DCC) outgrowth activity. PLoS One 9: e97258.
294. Yanik, M. F., H. Cinar, H. N. Cinar, A. D. Chisholm, Y. Jin et al., 2004 Neurosurgery: functional regeneration after laser axotomy. Nature 432: 822.
295. Yanik, M. F., H. Cinar, H. N. Cinar, A. Gibby, A. D. Chisholm et al., 2006 Nerve regeneration in Caenorhabditis elegans after femtosecond laser axotomy. IEEE J. Sel. Top. Quantum Electron. 12: 1283–1290.
296. Yaniv, S. P., N. Issman-Zecharya, M. Oren-Suissa, B. Podbilewicz, and O. Schuldiner, 2012 Axon regrowth during development and regeneration following injury share molecular mechanisms. Curr. Biol. 22: 1774–1782.
297. Yee, C. S., S. S. Sybingco, V. Serdetchania, G. Kholkina, M. Bueno de Mesquita et al., 2011 ENU-3 is a novel motor axon outgrowth and guidance protein in C. elegans. Dev. Biol. 352: 243–253.
298. Yoshimura, S., J. I. Murray, Y. Lu, R. H. Waterston, and S. Shaham, 2008 mls-2 and vab-3 Control glia development, hlh-17/Olig expression and glia-dependent neurite extension in C. elegans. Development 135: 2263–2275.
299. Yu, T. W., J. C. Hao, W. Lim, M. Tessier-Lavigne, and C. I. Bargmann, 2002 Shared receptors in axon guidance: SAX-3/robo signals via UNC-34/enabled and a netrin-independent UNC-40/DCC function. Nat. Neurosci. 5: 1147–1154.
300. Zallen, J. A., S. A. Kirch, and C. I. Bargmann, 1999 Genes required for axon pathfinding and extension in the C. elegans nerve ring. Development 126: 3679–3692.
301. Zhen, M., X. Huang, B. Bamber, and Y. Jin, 2000 Regulation of presynaptic terminal organization by C. elegans RPM-1, a putative guanine nucleotide exchanger with a RING-H2 finger domain. Neuron 26: 331–343.
302. Zhou, S., K. Opperman, X. Wang, and L. Chen, 2008 unc-44 Ankyrin and stn-2 gamma-syntrophin regulate sax-7 L1CAM function in maintaining neuronal positioning in Caenorhabditis elegans. Genetics 180: 1429–1443.
303. Ziel, J. W., E. J. Hagedorn, A. Audhya, and D. R. Sherwood, 2009 UNC-6 (netrin) orients the invasive membrane of the anchor cell in C. elegans. Nat. Cell Biol. 11: 183–189.
304. Zou, Y., H. Chiu, A. Zinovyeva, V. Ambros, C. F. Chuang et al., 2013 Developmental decline in neuronal regeneration by the progressive change of two intrinsic timers. Science 340: 372–376.