Neuronal Target Identification Requires AHA-1-Mediated Fine-Tuning of Wnt Signaling in

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Electrical synaptic transmission through gap junctions is a vital mode of intercellular communication in the nervous system. The mechanism by which reciprocal target cells find each other during the formation of gap junctions, however, is poorly understood. Here we show that gap junctions are formed between BDU interneurons and PLM mechanoreceptors in C. elegans and the connectivity of BDU with PLM is influenced by Wnt signaling. We further identified two PAS-bHLH family transcription factors, AHA-1 and AHR-1, which function cell-autonomously within BDU and PLM to facilitate the target identification process. aha-1 and ahr-1 act genetically upstream of cam-1. CAM-1, a membrane-bound receptor tyrosine kinase, is present on both BDU and PLM cells and likely serves as a Wnt antagonist. By binding to a cis-regulatory element in the cam-1 promoter, AHA-1 enhances cam-1 transcription. Our study reveals a Wnt-dependent fine-tuning mechanism that is crucial for mutual target cell identification during the formation of gap junction connections.

Vyšlo v časopise: Neuronal Target Identification Requires AHA-1-Mediated Fine-Tuning of Wnt Signaling in. PLoS Genet 9(6): e32767. doi:10.1371/journal.pgen.1003618
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003618

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Zdroje

1. DicksonBJ (2002) Molecular mechanisms of axon guidance. Science 298: 1959–1964.

2. LyuksyutovaAI, LuCC, MilanesioN, KingLA, GuoN, et al. (2003) Anterior-posterior guidance of commissural axons by Wnt-frizzled signaling. Science 302: 1984–1988.

3. CharronF, SteinE, JeongJ, McMahonAP, Tessier-LavigneM (2003) The morphogen sonic hedgehog is an axonal chemoattractant that collaborates with netrin-1 in midline axon guidance. Cell 113: 11–23.

4. FannonAM, ColmanDR (1996) A model for central synaptic junctional complex formation based on the differential adhesive specificities of the cadherins. Neuron 17: 423–434.

5. ShapiroL, LoveJ, ColmanDR (2007) Adhesion molecules in the nervous system: structural insights into function and diversity. Annu Rev Neurosci 30: 451–474.

6. WhiteJG, SouthgateE, ThomsonJN (1992) Mutations in the Caenorhabditis elegans unc-4 gene alter the synaptic input to ventral cord motor neurons. Nature 355: 838–841.

7. MillerDM, ShenMM, ShamuCE, BurglinTR, RuvkunG, et al. (1992) C. elegans unc-4 gene encodes a homeodomain protein that determines the pattern of synaptic input to specific motor neurons. Nature 355: 841–845.

8. WinnierAR, MeirJY, RossJM, TavernarakisN, DriscollM, et al. (1999) UNC-4/UNC-37-dependent repression of motor neuron-specific genes controls synaptic choice in Caenorhabditis elegans. Genes Dev 13: 2774–2786.

9. Von StetinaSE, FoxRM, WatkinsKL, StarichTA, ShawJE, et al. (2007) UNC-4 represses CEH-12/HB9 to specify synaptic inputs to VA motor neurons in C. elegans. Genes Dev 21: 332–346.

10. SchneiderJ, SkeltonRL, Von StetinaSE, MiddelkoopTC, van OudenaardenA, et al. (2012) UNC-4 antagonizes Wnt signaling to regulate synaptic choice in the C. elegans motor circuit. Development 139: 2234–2245.

11. NakamuraH, O'LearyDD (1989) Inaccuracies in initial growth and arborization of chick retinotectal axons followed by course corrections and axon remodeling to develop topographic order. J Neurosci 9: 3776–3795.

12. ChengHJ, NakamotoM, BergemannAD, FlanaganJG (1995) Complementary gradients in expression and binding of ELF-1 and Mek4 in development of the topographic retinotectal projection map. Cell 82: 371–381.

13. Colon-RamosDA, MargetaMA, ShenK (2007) Glia promote local synaptogenesis through UNC-6 (netrin) signaling in C. elegans. Science 318: 103–106.

14. ZouY (2004) Wnt signaling in axon guidance. Trends Neurosci 27: 528–532.

15. KlassenMP, ShenK (2007) Wnt signaling positions neuromuscular connectivity by inhibiting synapse formation in C. elegans. Cell 130: 704–716.

16. HikasaH, ShibataM, HirataniI, TairaM (2002) The Xenopus receptor tyrosine kinase Xror2 modulates morphogenetic movements of the axial mesoderm and neuroectoderm via Wnt signaling. Development 129: 5227–5239.

17. MikelsAJ, NusseR (2006) Purified Wnt5a protein activates or inhibits beta-catenin-TCF signaling depending on receptor context. PLoS Biol 4: e115.

18. GreenJL, InoueT, SternbergPW (2007) The C. elegans ROR receptor tyrosine kinase, CAM-1, non-autonomously inhibits the Wnt pathway. Development 134: 4053–4062.

19. ForresterWC, KimC, GarrigaG (2004) The Caenorhabditis elegans Ror RTK CAM-1 inhibits EGL-20/Wnt signaling in cell migration. Genetics 168: 1951–1962.

20. 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.

21. SongS, ZhangB, SunH, LiX, XiangY, et al. (2010) A Wnt-Frz/Ror-Dsh pathway regulates neurite outgrowth in Caenorhabditis elegans. PLoS Genet 6: e1001056.

22. HoHY, SusmanMW, BikoffJB, RyuYK, JonasAM, et al. (2012) Wnt5a-Ror-Dishevelled signaling constitutes a core developmental pathway that controls tissue morphogenesis. Proc Natl Acad Sci U S A 109: 4044–4051.

23. CruciatCM, NiehrsC (2013) Secreted and transmembrane Wnt inhibitors and activators. Cold Spring Harb Perspect Med 3: a015081.

24. FantauzzoKA, ChristianoAM (2012) Trps1 activates a network of secreted Wnt inhibitors and transcription factors crucial to vibrissa follicle morphogenesis. Development 139: 203–214.

25. ZhongY, WangZ, FuB, PanF, YachidaS, et al. (2011) GATA6 activates Wnt signaling in pancreatic cancer by negatively regulating the Wnt antagonist Dickkopf-1. PLoS One 6: e22129.

26. ShenC, NettletonD, JiangM, KimSK, Powell-CoffmanJA (2005) Roles of the HIF-1 hypoxia-inducible factor during hypoxia response in Caenorhabditis elegans. J Biol Chem 280: 20580–20588.

27. WhiteJG, SouthgateE, ThomsonJN, BrennerS (1986) The structure of the nervous system of the nematode Caenorhabditis elegans. Philos Trans R Soc Lond B Biol Sci 314: 1–340.

28. ChalfieM, SulstonJ (1981) Developmental genetics of the mechanosensory neurons of Caenorhabditis elegans. Dev Biol 82: 358–370.

29. YuanJY, HorvitzHR (1990) The Caenorhabditis elegans genes ced-3 and ced-4 act cell autonomously to cause programmed cell death. Dev Biol 138: 33–41.

30. YuanJ, ShahamS, LedouxS, EllisHM, HorvitzHR (1993) The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme. Cell 75: 641–652.

31. MahoneyTR, LiuQ, ItohT, LuoS, HadwigerG, et al. (2006) Regulation of synaptic transmission by RAB-3 and RAB-27 in Caenorhabditis elegans. Mol Biol Cell 17: 2617–2625.

32. AltunZF, ChenB, WangZW, HallDH (2009) High resolution map of Caenorhabditis elegans gap junction proteins. Dev Dyn 238: 1936–1950.

33. ChenB, LiuQ, GeQ, XieJ, WangZW (2007) UNC-1 regulates gap junctions important to locomotion in C. elegans. Curr Biol 17: 1334–1339.

34. StarichTA, XuJ, SkerrettIM, NicholsonBJ, ShawJE (2009) Interactions between innexins UNC-7 and UNC-9 mediate electrical synapse specificity in the Caenorhabditis elegans locomotory nervous system. Neural Dev 4: 16.

35. CoudreuseDY, RoelG, BetistMC, DestreeO, KorswagenHC (2006) Wnt gradient formation requires retromer function in Wnt-producing cells. Science 312: 921–924.

36. PrasadBC, ClarkSG (2006) Wnt signaling establishes anteroposterior neuronal polarity and requires retromer in C. elegans. Development 133: 1757–1766.

37. HilliardMA, BargmannCI (2006) Wnt signals and frizzled activity orient anterior-posterior axon outgrowth in C. elegans. Dev Cell 10: 379–390.

38. ForresterWC, DellM, PerensE, GarrigaG (1999) A C. elegans Ror receptor tyrosine kinase regulates cell motility and asymmetric cell division. Nature 400: 881–885.

39. ZinovyevaAY, ForresterWC (2005) The C. elegans Frizzled CFZ-2 is required for cell migration and interacts with multiple Wnt signaling pathways. Dev Biol 285: 447–461.

40. EisenmannDM (2005) Wnt signaling. WormBook 1–17.

41. HahnME (2002) Aryl hydrocarbon receptors: diversity and evolution. Chem Biol Interact 141: 131–160.

42. 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.

43. QinH, Powell-CoffmanJA (2004) The Caenorhabditis elegans aryl hydrocarbon receptor, AHR-1, regulates neuronal development. Dev Biol 270: 64–75.

44. JiangH, GuoR, Powell-CoffmanJA (2001) The Caenorhabditis elegans hif-1 gene encodes a bHLH-PAS protein that is required for adaptation to hypoxia. Proc Natl Acad Sci U S A 98: 7916–7921.

45. FinneyM, RuvkunG (1990) The unc-86 gene product couples cell lineage and cell identity in C. elegans. Cell 63: 895–905.

46. SogawaK, Numayama-TsurutaK, TakahashiT, MatsushitaN, MiuraC, et al. (2004) A novel induction mechanism of the rat CYP1A2 gene mediated by Ah receptor-Arnt heterodimer. Biochem Biophys Res Commun 318: 746–755.

47. GalarretaM, HestrinS (1999) A network of fast-spiking cells in the neocortex connected by electrical synapses. Nature 402: 72–75.

48. GibsonJR, BeierleinM, ConnorsBW (1999) Two networks of electrically coupled inhibitory neurons in neocortex. Nature 402: 75–79.

49. ChesireDR, DunnTA, EwingCM, LuoJ, IsaacsWB (2004) Identification of aryl hydrocarbon receptor as a putative Wnt/beta-catenin pathway target gene in prostate cancer cells. Cancer Res 64: 2523–2533.

50. ProchazkovaJ, KabatkovaM, BryjaV, UmannovaL, BernatikO, et al. (2011) The interplay of the aryl hydrocarbon receptor and beta-catenin alters both AhR-dependent transcription and Wnt/beta-catenin signaling in liver progenitors. Toxicol Sci 122: 349–360.

51. ZhaoS, KannoY, NakayamaM, MakimuraM, OharaS, et al. (2012) Activation of the aryl hydrocarbon receptor represses mammosphere formation in MCF-7 cells. Cancer Lett 317: 192–198.

52. MathewLK, SenguptaSS, LaduJ, AndreasenEA, TanguayRL (2008) Crosstalk between AHR and Wnt signaling through R-Spondin1 impairs tissue regeneration in zebrafish. FASEB J 22: 3087–3096.

53. PengG, WesterfieldM (2006) Lhx5 promotes forebrain development and activates transcription of secreted Wnt antagonists. Development 133: 3191–3200.

54. KimBM, BuchnerG, MiletichI, SharpePT, ShivdasaniRA (2005) The stomach mesenchymal transcription factor Barx1 specifies gastric epithelial identity through inhibition of transient Wnt signaling. Dev Cell 8: 611–622.

55. ChalfieM, SulstonJE, WhiteJG, SouthgateE, ThomsonJN, et al. (1985) The neural circuit for touch sensitivity in Caenorhabditis elegans. J Neurosci 5: 956–964.

56. FurshpanEJ, PotterDD (1957) Mechanism of nerve-impulse transmission at a crayfish synapse. Nature 180: 342–343.

57. PeinadoA, YusteR, KatzLC (1993) Extensive dye coupling between rat neocortical neurons during the period of circuit formation. Neuron 10: 103–114.

58. BrennerS (1974) The genetics of Caenorhabditis elegans. Genetics 77: 71–94.

59. SimmerF, TijstermanM, ParrishS, KoushikaSP, NonetML, et al. (2002) Loss of the putative RNA-directed RNA polymerase RRF-3 makes C. elegans hypersensitive to RNAi. Curr Biol 12: 1317–1319.

60. NonetML, GrundahlK, MeyerBJ, RandJB (1993) Synaptic function is impaired but not eliminated in C. elegans mutants lacking synaptotagmin. Cell 73: 1291–1305.

61. ZhongM, NiuW, LuZJ, SarovM, MurrayJI, et al. (2010) Genome-wide identification of binding sites defines distinct functions for Caenorhabditis elegans PHA-4/FOXA in development and environmental response. PLoS Genet 6: e1000848.