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A Wnt-Frz/Ror-Dsh Pathway Regulates Neurite Outgrowth in


One of the challenges to understand the organization of the nervous system has been to determine how axon guidance molecules govern axon outgrowth. Through an unbiased genetic screen, we identified a conserved Wnt pathway which is crucial for anterior-posterior (A/P) outgrowth of neurites from RME head motor neurons in Caenorhabditis elegans. The pathway is composed of the Wnt ligand CWN-2, the Frizzled receptors CFZ-2 and MIG-1, the co-receptor CAM-1/Ror, and the downstream component Dishevelled/DSH-1. Among these, CWN-2 acts as a local attractive cue for neurite outgrowth, and its activity can be partially substituted with other Wnts, suggesting that spatial distribution plays a role in the functional specificity of Wnts. As a co-receptor, CAM-1 functions cell-autonomously in neurons and, together with CFZ-2 and MIG-1, transmits the Wnt signal to downstream effectors. Yeast two-hybrid screening identified DSH-1 as a binding partner for CAM-1, indicating that CAM-1 could facilitate CWN-2/Wnt signaling by its physical association with DSH-1. Our study reveals an important role of a Wnt-Frz/Ror-Dsh pathway in regulating neurite A/P outgrowth.


Vyšlo v časopise: A Wnt-Frz/Ror-Dsh Pathway Regulates Neurite Outgrowth in. PLoS Genet 6(8): e32767. doi:10.1371/journal.pgen.1001056
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1001056

Souhrn

One of the challenges to understand the organization of the nervous system has been to determine how axon guidance molecules govern axon outgrowth. Through an unbiased genetic screen, we identified a conserved Wnt pathway which is crucial for anterior-posterior (A/P) outgrowth of neurites from RME head motor neurons in Caenorhabditis elegans. The pathway is composed of the Wnt ligand CWN-2, the Frizzled receptors CFZ-2 and MIG-1, the co-receptor CAM-1/Ror, and the downstream component Dishevelled/DSH-1. Among these, CWN-2 acts as a local attractive cue for neurite outgrowth, and its activity can be partially substituted with other Wnts, suggesting that spatial distribution plays a role in the functional specificity of Wnts. As a co-receptor, CAM-1 functions cell-autonomously in neurons and, together with CFZ-2 and MIG-1, transmits the Wnt signal to downstream effectors. Yeast two-hybrid screening identified DSH-1 as a binding partner for CAM-1, indicating that CAM-1 could facilitate CWN-2/Wnt signaling by its physical association with DSH-1. Our study reveals an important role of a Wnt-Frz/Ror-Dsh pathway in regulating neurite A/P outgrowth.


Zdroje

1. Tessier-LavigneM

GoodmanCS

1996 The molecular biology of axon guidance. Science 274 1123 1133

2. DicksonBJ

2002 Molecular mechanisms of axon guidance. Science 298 1959 1964

3. YuTW

BargmannCI

2001 Dynamic regulation of axon guidance. Nat Neurosci 4 Suppl 1169 1176

4. HuberAB

KolodkinAL

GintyDD

CloutierJF

2003 Signaling at the growth cone: ligand-receptor complexes and the control of axon growth and guidance. Annu Rev Neurosci 26 509 563

5. ZouY

2004 Wnt signaling in axon guidance. Trends Neurosci 27 528 532

6. MontcouquiolM

CrenshawEB3rd

KelleyMW

2006 Noncanonical Wnt signaling and neural polarity. Annu Rev Neurosci 29 363 386

7. LyuksyutovaAI

LuCC

MilanesioN

KingLA

GuoN

2003 Anterior-posterior guidance of commissural axons by Wnt-frizzled signaling. Science 302 1984 1988

8. WolfAM

LyuksyutovaAI

FenstermakerAG

ShaferB

LoCG

2008 Phosphatidylinositol-3-kinase-atypical protein kinase C signaling is required for Wnt attraction and anterior-posterior axon guidance. J Neurosci 28 3456 3467

9. KeebleTR

HalfordMM

SeamanC

KeeN

MachedaM

2006 The Wnt receptor Ryk is required for Wnt5a-mediated axon guidance on the contralateral side of the corpus callosum. J Neurosci 26 5840 5848

10. YoshikawaS

McKinnonRD

KokelM

ThomasJB

2003 Wnt-mediated axon guidance via the Drosophila Derailed receptor. Nature 422 583 588

11. EisenmannD

2005 Wnt signaling. In The C elegans Research Community WormBook

12. HermanMA

VassilievaLL

HorvitzHR

ShawJE

HermanRK

1995 The C. elegans gene lin-44, which controls the polarity of certain asymmetric cell divisions, encodes a Wnt protein and acts cell nonautonomously. Cell 83 101 110

13. WhangboJ

KenyonC

1999 A Wnt signaling system that specifies two patterns of cell migration in C. elegans. Mol Cell 4 851 858

14. HayashiY

HirotsuT

IwataR

Kage-NakadaiE

KunitomoH

2009 A trophic role for Wnt-Ror kinase signaling during developmental pruning in Caenorhabditis elegans. Nat Neurosci 12 981 987

15. HilliardMA

BargmannCI

2006 Wnt signals and frizzled activity orient anterior-posterior axon outgrowth in C. elegans. Dev Cell 10 379 390

16. KennerdellJR

FetterRD

BargmannCI

2009 Wnt-Ror signaling to SIA and SIB neurons directs anterior axon guidance and nerve ring placement in C. elegans. Development 136 3801 3810

17. PanCL

HowellJE

ClarkSG

HilliardM

CordesS

2006 Multiple Wnts and frizzled receptors regulate anteriorly directed cell and growth cone migrations in Caenorhabditis elegans. Dev Cell 10 367 377

18. SilhankovaM

KorswagenHC

2007 Migration of neuronal cells along the anterior-posterior body axis of C. elegans: Wnts are in control. Curr Opin Genet Dev 17 320 325

19. ZinovyevaAY

YamamotoY

SawaH

ForresterWC

2008 Complex network of Wnt signaling regulates neuronal migrations during Caenorhabditis elegans development. Genetics 179 1357 1371

20. SulstonJE

SchierenbergE

WhiteJG

ThomsonJN

1983 The embryonic cell lineage of the nematode Caenorhabditis elegans. Dev Biol 100 64 119

21. HuangX

Powell-CoffmanJA

JinY

2004 The AHR-1 aryl hydrocarbon receptor and its co-factor the AHA-1 aryl hydrocarbon receptor nuclear translocator specify GABAergic neuron cell fate in C. elegans. Development 131 819 828

22. HuangX

ChengHJ

Tessier-LavigneM

JinY

2002 MAX-1, a novel PH/MyTH4/FERM domain cytoplasmic protein implicated in netrin-mediated axon repulsion. Neuron 34 563 576

23. JinY

HoskinsR

HorvitzHR

1994 Control of type-D GABAergic neuron differentiation by C. elegans UNC-30 homeodomain protein. Nature 372 780 783

24. EastmanC

HorvitzHR

JinY

1999 Coordinated transcriptional regulation of the UNC-25 glutamic acid decarboxylase and the UNC-47 GABA vesicular transporter by the Caenorhabditis elegans UNC-30 homeodomain protein. J Neurosci 19 6225 6234

25. IshiiN

WadsworthWG

SternBD

CulottiJG

HedgecockEM

1992 UNC-6, a laminin-related protein, guides cell and pioneer axon migrations in C. elegans. Neuron 9 873 881

26. HaoJC

YuTW

FujisawaK

CulottiJG

Gengyo-AndoK

2001 C. elegans Slit acts in midline, dorsal-ventral, and anterior-posterior guidance via the SAX-3/Robo receptor. Neuron 32 25 38

27. GuptaBP

WangM

SternbergPW

2003 The C. elegans LIM homeobox gene lin-11 specifies multiple cell fates during vulval development. Development 130 2589 2601

28. HobertO

TessmarK

RuvkunG

1999 The Caenorhabditis elegans lim-6 LIM homeobox gene regulates neurite outgrowth and function of particular GABAergic neurons. Development 126 1547 1562

29. WhiteJG

SouthgateE

ThomsonJN

BrennerS

1976 The structure of the ventral nerve cord of Caenorhabditis elegans. Philos Trans R Soc Lond B Biol Sci 275 327 348

30. InoueT

OzHS

WilandD

GharibS

DeshpandeR

2004 C. elegans LIN-18 is a Ryk ortholog and functions in parallel to LIN-17/Frizzled in Wnt signaling. Cell 118 795 806

31. BurdineRD

BrandaCS

SternMJ

1998 EGL-17(FGF) expression coordinates the attraction of the migrating sex myoblasts with vulval induction in C. elegans. Development 125 1083 1093

32. ForresterWC

DellM

PerensE

GarrigaG

1999 A C. elegans Ror receptor tyrosine kinase regulates cell motility and asymmetric cell division. Nature 400 881 885

33. KogaM

Take-uchiM

TameishiT

OhshimaY

1999 Control of DAF-7 TGF-(alpha) expression and neuronal process development by a receptor tyrosine kinase KIN-8 in Caenorhabditis elegans. Development 126 5387 5398

34. LiuY

ShiJ

LuCC

WangZB

LyuksyutovaAI

2005 Ryk-mediated Wnt repulsion regulates posterior-directed growth of corticospinal tract. Nat Neurosci 8 1151 1159

35. GreenJL

InoueT

SternbergPW

2007 The C. elegans ROR receptor tyrosine kinase, CAM-1, non-autonomously inhibits the Wnt pathway. Development 134 4053 4062

36. ForresterWC

KimC

GarrigaG

2004 The Caenorhabditis elegans Ror RTK CAM-1 inhibits EGL-20/Wnt signaling in cell migration. Genetics 168 1951 1962

37. CoudreuseDY

RoelG

BetistMC

DestreeO

KorswagenHC

2006 Wnt gradient formation requires retromer function in Wnt-producing cells. Science 312 921 924

38. PrasadBC

ClarkSG

2006 Wnt signaling establishes anteroposterior neuronal polarity and requires retromer in C. elegans. Development 133 1757 1766

39. IkedaS

KishidaS

YamamotoH

MuraiH

KoyamaS

1998 Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3beta and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin. EMBO J 17 1371 1384

40. MaroGS

KlassenMP

ShenK

2009 A beta-catenin-dependent Wnt pathway mediates anteroposterior axon guidance in C. elegans motor neurons. PLoS One 4 e4690 doi:10.1371/journal.pone.0004690

41. KlassenMP

ShenK

2007 Wnt signaling positions neuromuscular connectivity by inhibiting synapse formation in C. elegans. Cell 130 704 716

42. HedgecockEM

CulottiJG

HallDH

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

43. BrennerS

1974 The genetics of Caenorhabditis elegans. Genetics 77 71 94

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