Semaphorins pp 19-37 | Cite as

Semaphorin Regulation of Neural Circuit Assembly in the Central Nervous System

Chapter

Abstract

The assembly of neural circuits requires a wide array of molecular cues. These cues include secreted and transmembrane ligands and also the signaling receptors that together modulate axonal and dendritic morphology to promote functional neural connectivity during development. The semaphorin family of proteins and their various receptors serve this function. Many experiments demonstrate in vivo, and in multiple neural systems, how semaphorin-mediated regulation of neuronal morphology is critical for the regulation of neuronal connectivity. This system is nicely illustrated by recent work on semaphorin function in establishing neural connections in the olfactory and visual systems in both flies and mice. Further, semaphorins and their receptors regulate the elaboration of axon trajectories and precise targeting of these projections in the mammalian central nervous system, in addition to mediating axon pruning and also excitatory and inhibitory synaptogenesis. Taken together, these investigations into how semaphorins regulate neural connectivity provide insight into developmental mechanisms critical for neurite targeting, laminar-specific innervation, selective synapse formation, and neural circuit refinement.

Keywords

Neural circuits Semaphorin Neural development Plexin Axon guidance Dendritic morphology Visual system Olfactory system Hippocampus Cerebral cortex 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgments

Work in the authors’ laboratory is supported by the NIH (NINDS and NIMH) and the Howard Hughes Medical Institute. A.L.K. is an investigator of the Howard Hughes Medical Institute.

References

  1. Bagri A, Cheng HJ, Yaron A, Pleasure SJ, Tessier-Lavigne M (2003) Stereotyped pruning of long hippocampal axon branches triggered by retraction inducers of the semaphorin family. Cell 113(3):285–299CrossRefPubMedGoogle Scholar
  2. Bellon A, Luchino J, Haigh K, Rougon G, Haigh J, Chauvet S, Mann F (2010) VEGFR2 (KDR/Flk1) signaling mediates axon growth in response to semaphorin 3E in the developing brain. Neuron 66(2):205–219CrossRefPubMedGoogle Scholar
  3. Cafferty P, Yu L, Long H, Rao Y (2006) Semaphorin-1a functions as a guidance receptor in the Drosophila visual system. J Neurosci 26(15):3999–4003CrossRefPubMedGoogle Scholar
  4. Castellani V, Chedotal A, Schachner M, Faivre-Sarrailh C, Rougon G (2000) Analysis of the L1-deficient mouse phenotype reveals cross-talk between Sema3A and L1 signaling pathways in axonal guidance. Neuron 27(2):237–249CrossRefPubMedGoogle Scholar
  5. Chauvet S, Cohen S, Yoshida Y, Fekrane L, Livet J, Gayet O, Segu L, Buhot MC, Jessell TM, Henderson CE, Mann F (2007) Gating of Sema3E/PlexinD1 signaling by neuropilin-1 switches axonal repulsion to attraction during brain development. Neuron 56(5):807–822CrossRefPubMedCentralPubMedGoogle Scholar
  6. Cioni JM, Telley L, Saywell V, Cadilhac C, Jourdan C, Huber AB, Huang JZ, Jahannault-Talignani C, Ango F (2013) SEMA3A signaling controls layer-specific interneuron branching in the cerebellum. Curr Biol 23(10):850–861CrossRefPubMedGoogle Scholar
  7. Cloutier JF, Giger RJ, Koentges G, Dulac C, Kolodkin AL, Ginty DD (2002) Neuropilin-2 mediates axonal fasciculation, zonal segregation, but not axonal convergence, of primary accessory olfactory neurons. Neuron 33(6):877–892CrossRefPubMedGoogle Scholar
  8. Cloutier JF, Sahay A, Chang EC, Tessier-Lavigne M, Dulac C, Kolodkin AL, Ginty DD (2004) Differential requirements for semaphorin 3F and Slit-1 in axonal targeting, fasciculation, and segregation of olfactory sensory neuron projections. J Neurosci 24(41):9087–9096CrossRefPubMedGoogle Scholar
  9. Deck M, Lokmane L, Chauvet S, Mailhes C, Keita M, Niquille M, Yoshida M, Yoshida Y, Lebrand C, Mann F, Grove EA, Garel S (2013) Pathfinding of corticothalamic axons relies on a rendezvous with thalamic projections. Neuron 77(3):472–484CrossRefPubMedCentralPubMedGoogle Scholar
  10. Dell AL, Fried-Cassorla E, Xu H, Raper JA (2013) cAMP-induced expression of neuropilin1 promotes retinal axon crossing in the zebrafish optic chiasm. J Neurosci 33(27):11076–11088CrossRefPubMedCentralPubMedGoogle Scholar
  11. Demyanenko GP, Riday TT, Tran TS, Dalal J, Darnell EP, Brennaman LH, Sakurai T, Grumet M, Philpot BD, Maness PF (2011) NrCAM deletion causes topographic mistargeting of thalamocortical axons to the visual cortex and disrupts visual acuity. J Neurosci 31(4):1545–1558CrossRefPubMedCentralPubMedGoogle Scholar
  12. Ding JB, Oh WJ, Sabatini BL, Gu C (2012) Semaphorin 3E-Plexin-D1 signaling controls pathway-specific synapse formation in the striatum. Nat Neurosci 15(2):215–223CrossRefGoogle Scholar
  13. Erskine L, Reijntjes S, Pratt T, Denti L, Schwarz Q, Vieira JM, Alakakone B, Shewan D, Ruhrberg C (2011) VEGF signaling through neuropilin 1 guides commissural axon crossing at the optic chiasm. Neuron 70(5):951–965CrossRefPubMedCentralPubMedGoogle Scholar
  14. Falk J, Bechara A, Fiore R, Nawabi H, Zhou H, Hoyo-Becerra C, Bozon M, Rougon G, Grumet M, Puschel AW, Sanes JR, Castellani V (2005) Dual functional activity of semaphorin 3B is required for positioning the anterior commissure. Neuron 48(1):63–75CrossRefPubMedGoogle Scholar
  15. Gu C, Rodriguez ER, Reimert DV, Shu T, Fritzsch B, Richards LJ, Kolodkin AL, Ginty DD (2003) Neuropilin-1 conveys semaphorin and VEGF signaling during neural and cardiovascular development. Dev Cell 5(1):45–57CrossRefPubMedCentralPubMedGoogle Scholar
  16. Gu C, Yoshida Y, Livet J, Reimert DV, Mann F, Merte J, Henderson CE, Jessell TM, Kolodkin AL, Ginty DD (2005) Semaphorin 3E and plexin-D1 control vascular pattern independently of neuropilins. Science 307(5707):265–268CrossRefPubMedGoogle Scholar
  17. Imai T, Suzuki M, Sakano H (2006) Odorant receptor-derived cAMP signals direct axonal targeting. Science 314(5799):657–661CrossRefPubMedGoogle Scholar
  18. Imai T, Yamazaki T, Kobayakawa R, Kobayakawa K, Abe T, Suzuki M, Sakano H (2009) Pre-target axon sorting establishes the neural map topography. Science 325(5940):585–590CrossRefPubMedGoogle Scholar
  19. Imai T, Sakano H, Vosshall LB (2010) Topographic mapping – the olfactory system. Cold Spring Harbor Perspect Biol 2(8):a001776CrossRefGoogle Scholar
  20. Jeong S, Juhaszova K, Kolodkin AL (2012) The control of semaphorin-1a-mediated reverse signaling by opposing pebble and RhoGAPp190 functions in drosophila. Neuron 76(4):721–734CrossRefPubMedCentralPubMedGoogle Scholar
  21. Joo WJ, Sweeney LB, Liang L, Luo L (2013) Linking cell fate, trajectory choice, and target selection: genetic analysis of Sema-2b in olfactory axon targeting. Neuron 78(4):673–686CrossRefPubMedCentralPubMedGoogle Scholar
  22. Kolk SM, Gunput RA, Tran TS, van den Heuvel DM, Prasad AA, Hellemons AJ, Adolfs Y, Ginty DD, Kolodkin AL, Burbach JP, Smidt MP, Pasterkamp RJ (2009) Semaphorin 3F is a bifunctional guidance cue for dopaminergic axons and controls their fasciculation, channeling, rostral growth, and intracortical targeting. J Neurosci 29(40):12542–12557CrossRefPubMedCentralPubMedGoogle Scholar
  23. Kolodkin AL, Matthes DJ, O’Connor TP, Patel NH, Admon A, Bentley D, Goodman CS (1992) Fasciclin IV: sequence, expression, and function during growth cone guidance in the grasshopper embryo. Neuron 9(5):831–845CrossRefPubMedGoogle Scholar
  24. Komiyama T, Sweeney LB, Schuldiner O, Garcia KC, Luo L (2007) Graded expression of semaphorin-1a cell-autonomously directs dendritic targeting of olfactory projection neurons. Cell 128(2):399–410CrossRefPubMedGoogle Scholar
  25. Kuwajima T, Yoshida Y, Takegahara N, Petros TJ, Kumanogoh A, Jessell TM, Sakurai T, Mason C (2012) Optic chiasm presentation of Semaphorin6D in the context of Plexin-A1 and Nr-CAM promotes retinal axon midline crossing. Neuron 74(4):676–690CrossRefPubMedCentralPubMedGoogle Scholar
  26. Kuzirian MS, Moore AR, Staudenmaier EK, Friedel RH, Paradis S (2013) The class 4 semaphorin Sema4D promotes the rapid assembly of GABAergic synapses in rodent hippocampus. J Neurosci 33(21):8961–8973CrossRefPubMedCentralPubMedGoogle Scholar
  27. Lattemann M, Zierau A, Schulte C, Seidl S, Kuhlmann B, Hummel T (2007) Semaphorin-1a controls receptor neuron-specific axonal convergence in the primary olfactory center of Drosophila. Neuron 53(2):169–184CrossRefPubMedGoogle Scholar
  28. Lefebvre JL, Kostadinov D, Chen WV, Maniatis T, Sanes JR (2012) Protocadherins mediate dendritic self-avoidance in the mammalian nervous system. Nature 488(7412):517–521CrossRefPubMedCentralPubMedGoogle Scholar
  29. Liu XB, Low LK, Jones EG, Cheng HJ (2005) Stereotyped axon pruning via plexin signaling is associated with synaptic complex elimination in the hippocampus. J Neurosci 25(40):9124–9134CrossRefPubMedGoogle Scholar
  30. Low LK, Liu XB, Faulkner RL, Coble J, Cheng HJ (2008) Plexin signaling selectively regulates the stereotyped pruning of corticospinal axons from visual cortex. Proc Natl Acad Sci U S A 105(23):8136–8141CrossRefPubMedCentralPubMedGoogle Scholar
  31. Matsuo T, Rossier DA, Kan C, Rodriguez I (2012) The wiring of Grueneberg ganglion axons is dependent on neuropilin 1. Development 139(15):2783–2791CrossRefPubMedGoogle Scholar
  32. Matsuoka RL, Chivatakarn O, Badea TC, Samuels IS, Cahill H, Katayama K, Kumar SR, Suto F, Chedotal A, Peachey NS, Nathans J, Yoshida Y, Giger RJ, Kolodkin AL (2011a) Class 5 transmembrane semaphorins control selective Mammalian retinal lamination and function. Neuron 71(3):460–473CrossRefPubMedCentralPubMedGoogle Scholar
  33. Matsuoka RL, Nguyen-Ba-Charvet KT, Parray A, Badea TC, Chedotal A, Kolodkin AL (2011b) Transmembrane semaphorin signalling controls laminar stratification in the mammalian retina. Nature 470(7333):259–263CrossRefPubMedCentralPubMedGoogle Scholar
  34. Matsuoka RL, Jiang Z, Samuels IS, Nguyen-Ba-Charvet KT, Sun LO, Peachey NS, Chedotal A, Yau KW, Kolodkin AL (2012) Guidance-cue control of horizontal cell morphology, lamination, and synapse formation in the mammalian outer retina. J Neurosci 32(20):6859–6868CrossRefPubMedCentralPubMedGoogle Scholar
  35. Nakashima A, Takeuchi H, Imai T, Saito H, Kiyonari H, Abe T, Chen M, Weinstein LS, Yu CR, Storm DR, Nishizumi H, Sakano H (2013) Agonist-independent GPCR activity regulates anterior-posterior targeting of olfactory sensory neurons. Cell 154(6):1314–1325CrossRefPubMedGoogle Scholar
  36. Paradis S, Harrar DB, Lin Y, Koon AC, Hauser JL, Griffith EC, Zhu L, Brass LF, Chen C, Greenberg ME (2007) An RNAi-based approach identifies molecules required for glutamatergic and GABAergic synapse development. Neuron 53(2):217–232CrossRefPubMedCentralPubMedGoogle Scholar
  37. Pecot MY, Tadros W, Nern A, Bader M, Chen Y, Zipursky SL (2013) Multiple interactions control synaptic layer specificity in the Drosophila visual system. Neuron 77(2):299–310CrossRefPubMedCentralPubMedGoogle Scholar
  38. Riccomagno MM, Hurtado A, Wang H, Macopson JG, Griner EM, Betz A, Brose N, Kazanietz MG, Kolodkin AL (2012) The RacGAP beta2-Chimaerin selectively mediates axonal pruning in the hippocampus. Cell 149(7):1594–1606CrossRefPubMedCentralPubMedGoogle Scholar
  39. Sakai JA, Halloran MC (2006) Semaphorin 3d guides laterality of retinal ganglion cell projections in zebrafish. Development 133(6):1035–1044CrossRefPubMedGoogle Scholar
  40. Sanes JR, Yamagata M (2009) Many paths to synaptic specificity. Annu Rev Cell Dev Biol 25:161–195CrossRefPubMedGoogle Scholar
  41. Sanes JR, Zipursky SL (2010) Design principles of insect and vertebrate visual systems. Neuron 66(1):15–36CrossRefPubMedCentralPubMedGoogle Scholar
  42. Schwarting GA, Kostek C, Ahmad N, Dibble C, Pays L, Puschel AW (2000) Semaphorin 3A is required for guidance of olfactory axons in mice. J Neurosci 20(20):7691–7697PubMedGoogle Scholar
  43. Schwarting GA, Raitcheva D, Crandall JE, Burkhardt C, Puschel AW (2004) Semaphorin 3A-mediated axon guidance regulates convergence and targeting of P2 odorant receptor axons. Eur J Neurosci 19(7):1800–1810CrossRefPubMedGoogle Scholar
  44. Sun LO, Brady CM, Cahill H, Al-Khindi T, Sakuta H, Dhande OS, Noda M, Huberman AD, Nathans J, Kolodkin AL (2015) Functional assembly of accessory optic system circuitry critical for compensatory eye movements. Neuron (in press)Google Scholar
  45. Sun LO, Jiang Z, Rivlin-Etzion M, Hand R, Brady CM, Matsuoka RL, Yau KW, Feller MB, Kolodkin AL (2013) On and off retinal circuit assembly by divergent molecular mechanisms. Science 342(6158):1241974CrossRefPubMedGoogle Scholar
  46. Suto F, Tsuboi M, Kamiya H, Mizuno H, Kiyama Y, Komai S, Shimizu M, Sanbo M, Yagi T, Hiromi Y, Chedotal A, Mitchell KJ, Manabe T, Fujisawa H (2007) Interactions between plexin-A2, plexin-A4, and semaphorin 6A control lamina-restricted projection of hippocampal mossy fibers. Neuron 53(4):535–547CrossRefPubMedGoogle Scholar
  47. Sweeney LB, Couto A, Chou YH, Berdnik D, Dickson BJ, Luo L, Komiyama T (2007) Temporal target restriction of olfactory receptor neurons by Semaphorin-1a/PlexinA-mediated axon-axon interactions. Neuron 53(2):185–200CrossRefPubMedGoogle Scholar
  48. Sweeney LB, Chou YH, Wu Z, Joo W, Komiyama T, Potter CJ, Kolodkin AL, Garcia KC, Luo L (2011) Secreted semaphorins from degenerating larval ORN axons direct adult projection neuron dendrite targeting. Neuron 72(5):734–747CrossRefPubMedCentralPubMedGoogle Scholar
  49. Tawarayama H, Yoshida Y, Suto F, Mitchell KJ, Fujisawa H (2010) Roles of semaphorin-6B and plexin-A2 in lamina-restricted projection of hippocampal mossy fibers. J Neurosci 30(20):7049–7060CrossRefPubMedCentralPubMedGoogle Scholar
  50. Toyofuku T, Zhang H, Kumanogoh A, Takegahara N, Suto F, Kamei J, Aoki K, Yabuki M, Hori M, Fujisawa H, Kikutani H (2004) Dual roles of Sema6D in cardiac morphogenesis through region-specific association of its receptor, Plexin-A1, with off-track and vascular endothelial growth factor receptor type 2. Genes Dev 18(4):435–447CrossRefPubMedCentralPubMedGoogle Scholar
  51. Tran TS, Kolodkin AL, Bharadwaj R (2007) Semaphorin regulation of cellular morphology. Annu Rev Cell Dev Biol 23:263–292CrossRefPubMedGoogle Scholar
  52. Tran TS, Rubio ME, Clem RL, Johnson D, Case L, Tessier-Lavigne M, Huganir RL, Ginty DD, Kolodkin AL (2009) Secreted semaphorins control spine distribution and morphogenesis in the postnatal CNS. Nature 462(7276):1065–1069CrossRefPubMedCentralPubMedGoogle Scholar
  53. Walz A, Rodriguez I, Mombaerts P (2002) Aberrant sensory innervation of the olfactory bulb in neuropilin-2 mutant mice. J Neurosci 22(10):4025–4035PubMedGoogle Scholar
  54. Walz A, Feinstein P, Khan M, Mombaerts P (2007) Axonal wiring of guanylate cyclase-D-expressing olfactory neurons is dependent on neuropilin 2 and semaphorin 3F. Development 134(22):4063–4072CrossRefPubMedGoogle Scholar
  55. Wright AG, Demyanenko GP, Powell A, Schachner M, Enriquez-Barreto L, Tran TS, Polleux F, Maness PF (2007) Close homolog of L1 and neuropilin 1 mediate guidance of thalamocortical axons at the ventral telencephalon. J Neurosci 27(50):13667–13679CrossRefPubMedGoogle Scholar
  56. Yu L, Zhou Y, Cheng S, Rao Y (2010) Plexin a-semaphorin-1a reverse signaling regulates photoreceptor axon guidance in Drosophila. J Neurosci 30(36):12151–12156CrossRefPubMedGoogle Scholar

Copyright information

© Springer Japan 2015

Authors and Affiliations

  1. 1.The Solomon H. Snyder Department of Neuroscience and Howard Hughes Medical InstituteThe Johns Hopkins University School of MedicineBaltimoreUSA

Personalised recommendations