growth cones


Summary: Bulbous enlargement of the growing tip of nerve axons and dendrites. They are crucial to neuronal development because of their pathfinding ability and their role in synaptogenesis.

Top Publications

  1. Hur E, Saijilafu -, Lee B, Kim S, Xu W, Zhou F. GSK3 controls axon growth via CLASP-mediated regulation of growth cone microtubules. Genes Dev. 2011;25:1968-81 pubmed publisher a MT plus end-binding protein, displays both plus end-binding and lattice-binding activities in nerve growth cones, and reveal that the two MT-binding activities regulate axon growth in an opposing manner: The lattice-binding ..
  2. Shigeoka T, Lu B, Holt C. Cell biology in neuroscience: RNA-based mechanisms underlying axon guidance. J Cell Biol. 2013;202:991-9 pubmed publisher
    Axon guidance plays a key role in establishing neuronal circuitry. The motile tips of growing axons, the growth cones, navigate by responding directionally to guidance cues that pattern the embryonic neural pathways via receptor-mediated ..
  3. Henle S, Wang G, Liang E, Wu M, Poo M, Henley J. Asymmetric PI(3,4,5)P3 and Akt signaling mediates chemotaxis of axonal growth cones. J Neurosci. 2011;31:7016-27 pubmed publisher
    ..Furthermore, patch-clamp recording from growth cones revealed that exogenous PI(3,4,5)P3 rapidly activated TRP (transient receptor potential) channels, and ..
  4. Akiyama H, Kamiguchi H. Phosphatidylinositol 3-kinase facilitates microtubule-dependent membrane transport for neuronal growth cone guidance. J Biol Chem. 2010;285:41740-8 pubmed publisher
    ..1,4,5-trisphosphate, triggered asymmetric transport of membrane vesicles from the center to the periphery of growth cones in a MT-dependent manner...
  5. Stagi M, Fogel A, Biederer T. SynCAM 1 participates in axo-dendritic contact assembly and shapes neuronal growth cones. Proc Natl Acad Sci U S A. 2010;107:7568-73 pubmed publisher
    Neuronal growth cones are highly motile structures that tip developing neurites and explore their surroundings before axo-dendritic contact and synaptogenesis...
  6. Toriyama M, Sakumura Y, Shimada T, Ishii S, Inagaki N. A diffusion-based neurite length-sensing mechanism involved in neuronal symmetry breaking. Mol Syst Biol. 2010;6:394 pubmed publisher
  7. Chernyshova Y, Leshchyns ka I, Hsu S, Schachner M, Sytnyk V. The neural cell adhesion molecule promotes FGFR-dependent phosphorylation and membrane targeting of the exocyst complex to induce exocytosis in growth cones. J Neurosci. 2011;31:3522-35 pubmed publisher the sec8 subunit of the exocyst complex and is required for efficient recruitment of the exocyst complex to growth cones. NCAM at the surface of growth cones induces Ca(2+)-dependent vesicle exocytosis, which is blocked by an ..
  8. Liu M, Nadar V, Kozielski F, Kozlowska M, Yu W, Baas P. Kinesin-12, a mitotic microtubule-associated motor protein, impacts axonal growth, navigation, and branching. J Neurosci. 2010;30:14896-906 pubmed publisher
    ..grow faster, more than doubles the frequency of microtubule transport in both directions in the axon, prevents growth cones from turning properly, and enhances the invasion of microtubules into filopodia...
  9. Cotrufo T, Perez Branguli F, Muhaisen A, Ros O, Andres R, Baeriswyl T, et al. A signaling mechanism coupling netrin-1/deleted in colorectal cancer chemoattraction to SNARE-mediated exocytosis in axonal growth cones. J Neurosci. 2011;31:14463-80 pubmed publisher migration and axonal guidance is the regulation of plasmalemma turnover and exocytosis in leading edges and growth cones. However, the cross talk mechanisms linking guidance receptors and membrane exocytosis are not understood...

More Information


  1. Eva R, Dassie E, Caswell P, Dick G, Ffrench Constant C, Norman J, et al. Rab11 and its effector Rab coupling protein contribute to the trafficking of beta 1 integrins during axon growth in adult dorsal root ganglion neurons and PC12 cells. J Neurosci. 2010;30:11654-69 pubmed publisher
    ..Rab11 colocalizes with alpha9 and other alpha integrins and with beta1 integrin in growth cones and axons, and immunopurified Rab11 vesicles contain alpha9 and beta1...
  2. Estrada Bernal A, Sanford S, Sosa L, Simon G, Hansen K, Pfenninger K. Functional complexity of the axonal growth cone: a proteomic analysis. PLoS ONE. 2012;7:e31858 pubmed publisher
    ..We performed an extensive proteomic analysis of axonal growth cones isolated from the brains of fetal Sprague-Dawley rats...
  3. Chacón M, Navarro A, Cuesto G, del Pino I, Scott R, Morales M, et al. Focal adhesion kinase regulates actin nucleation and neuronal filopodia formation during axonal growth. Development. 2012;139:3200-10 pubmed publisher
    The establishment of neural circuits depends on the ability of axonal growth cones to sense their surrounding environment en route to their target...
  4. Deinhardt K, Kim T, Spellman D, Mains R, Eipper B, Neubert T, et al. Neuronal growth cone retraction relies on proneurotrophin receptor signaling through Rac. Sci Signal. 2011;4:ra82 pubmed publisher
    ..neurotrophin nerve growth factor (NGF), we found that the precursor of NGF, proNGF, induced acute collapse of growth cones of cultured hippocampal neurons...
  5. Lamoureux P, Heidemann S, Martzke N, Miller K. Growth and elongation within and along the axon. Dev Neurobiol. 2010;70:135-49 pubmed publisher
    ..We found axons thinned during high rates of elongation and thickened when the growth cones were stationary...
  6. Jang K, Kim M, Feltrin D, Jeon N, Suh K, Pertz O. Two distinct filopodia populations at the growth cone allow to sense nanotopographical extracellular matrix cues to guide neurite outgrowth. PLoS ONE. 2010;5:e15966 pubmed publisher
    ..Our work provides insight in how neuronal growth cones can sense geometric ECM cues. This has not been accessible previously using routine 2D culture systems.
  7. Jung H, O Hare C, Holt C. Translational regulation in growth cones. Curr Opin Genet Dev. 2011;21:458-64 pubmed publisher
    Axonal growth cones (GCs) steer in response to extrinsic cues using mechanisms that include local protein synthesis. This adaptive form of gene regulation occurs with spatial precision and depends on subcellular mRNA localisation...
  8. Vitriol E, Zheng J. Growth cone travel in space and time: the cellular ensemble of cytoskeleton, adhesion, and membrane. Neuron. 2012;73:1068-81 pubmed publisher
    b>Growth cones, found at the tip of axonal projections, are the sensory and motile organelles of developing neurons that enable axon pathfinding and target recognition for precise wiring of the neural circuitry...
  9. Nadar V, Lin S, Baas P. Microtubule redistribution in growth cones elicited by focal inactivation of kinesin-5. J Neurosci. 2012;32:5783-94 pubmed publisher
    In order for growth cones to turn, microtubules from the central domain must preferentially invade the peripheral domain in the direction of the turn...
  10. Yang Q, Zhang X, Pollard T, Forscher P. Arp2/3 complex-dependent actin networks constrain myosin II function in driving retrograde actin flow. J Cell Biol. 2012;197:939-56 pubmed publisher
  11. Takano T, Tomomura M, Yoshioka N, Tsutsumi K, Terasawa Y, Saito T, et al. LMTK1/AATYK1 is a novel regulator of axonal outgrowth that acts via Rab11 in a Cdk5-dependent manner. J Neurosci. 2012;32:6587-99 pubmed publisher
    ..Thus, LMTK1 can negatively control axonal outgrowth by regulating Rab11A activity in a Cdk5-dependent manner, and Cdk5-LMTK1-Rab11 is a novel signaling pathway involved in axonal outgrowth. ..
  12. Gallo G. The cytoskeletal and signaling mechanisms of axon collateral branching. Dev Neurobiol. 2011;71:201-20 pubmed publisher
    ..Linking the activation of signaling pathways to specific proteins that directly regulate the axonal cytoskeleton underlying the formation of collateral branches remains a frontier in the field. ..
  13. Tojima T, Hines J, Henley J, Kamiguchi H. Second messengers and membrane trafficking direct and organize growth cone steering. Nat Rev Neurosci. 2011;12:191-203 pubmed publisher
    ..and cyclic nucleotides - shapes cue-derived information into either attractive or repulsive signals that steer growth cones bidirectionally...
  14. PERRON J, Dodd J. Inductive specification and axonal orientation of spinal neurons mediated by divergent bone morphogenetic protein signaling pathways. Neural Dev. 2011;6:36 pubmed publisher
    ..A model is proposed whereby selective engagement of BMP receptor subunits underlies choice of signaling pathway. ..
  15. Welshhans K, Bassell G. Netrin-1-induced local ?-actin synthesis and growth cone guidance requires zipcode binding protein 1. J Neurosci. 2011;31:9800-13 pubmed publisher
    Local ?-actin synthesis in growth cones of developing axons plays an important role in growth cone steering; however, the mRNA binding proteins required for this process are unknown...
  16. Nozumi M, Togano T, Takahashi Niki K, Lu J, Honda A, Taoka M, et al. Identification of functional marker proteins in the mammalian growth cone. Proc Natl Acad Sci U S A. 2009;106:17211-6 pubmed publisher
    ..Here, we successfully used a proteomic approach to identify 945 proteins present in developing rat forebrain growth cones, including highly abundant, membrane-associated and actin-associated proteins...
  17. Myers J, Santiago Medina M, Gomez T. Regulation of axonal outgrowth and pathfinding by integrin-ECM interactions. Dev Neurobiol. 2011;71:901-23 pubmed publisher
    ..Integrin receptors on growth cones associate with a number of cytosolic adaptor and signaling proteins that regulate cytoskeletal dynamics and ..
  18. Shim S, Yuan J, Kim J, Zeng W, Huang G, Milshteyn A, et al. Peptidyl-prolyl isomerase FKBP52 controls chemotropic guidance of neuronal growth cones via regulation of TRPC1 channel opening. Neuron. 2009;64:471-83 pubmed publisher
    ..stimulus-dependent TRPC1 gating through isomerization, which is required for chemotropic turning of neuronal growth cones to netrin-1 and myelin-associated glycoprotein and for netrin-1/DCC-dependent midline axon guidance of ..
  19. Laishram J, Kondra S, Avossa D, Migliorini E, Lazzarino M, Torre V. A morphological analysis of growth cones of DRG neurons combining atomic force and confocal microscopy. J Struct Biol. 2009;168:366-77 pubmed publisher
    We have analyzed the morphology of growth cones of differentiating neurons from rat dorsal root ganglia (DRG) with conventional Laser Scanning Confocal Microscopy (LSCM) and Atomic Force Microscopy (AFM)...
  20. Donnelly C, Willis D, Xu M, Tep C, Jiang C, Yoo S, et al. Limited availability of ZBP1 restricts axonal mRNA localization and nerve regeneration capacity. EMBO J. 2011;30:4665-77 pubmed publisher
    ..These data support a direct role for ZBP1 in transport and translation of mRNA cargos in axonal regeneration in vitro and in vivo. ..
  21. Spillane M, Ketschek A, Donnelly C, Pacheco A, TWISS J, Gallo G. Nerve growth factor-induced formation of axonal filopodia and collateral branches involves the intra-axonal synthesis of regulators of the actin-nucleating Arp2/3 complex. J Neurosci. 2012;32:17671-89 pubmed publisher
    ..Finally, we present experimental evidence of axonal mRNA translation in sensory axons in the living embryonic spinal cord...
  22. Ahmed Z, Douglas M, Read M, Berry M, Logan A. Citron kinase regulates axon growth through a pathway that converges on cofilin downstream of RhoA. Neurobiol Dis. 2011;41:421-9 pubmed publisher
    ..We conclude that Citron-K regulates actin polymerisation downstream of RhoA and may offer a potentially novel therapeutic approach for promoting CNS axon regeneration. ..
  23. Hur E, Yang I, Kim D, Byun J, Saijilafu -, Xu W, et al. Engineering neuronal growth cones to promote axon regeneration over inhibitory molecules. Proc Natl Acad Sci U S A. 2011;108:5057-62 pubmed publisher
    ..Together, our study proposes NMII and growth cone cytoskeletal components as effective targets for promoting axon regeneration. ..
  24. Ma L, Greenwood J, Schachner M. CRP1, a protein localized in filopodia of growth cones, is involved in dendritic growth. J Neurosci. 2011;31:16781-91 pubmed publisher
    ..Here, we report that CRP1 colocalizes with actin in the filopodia of growth cones in cultured rat hippocampal neurons...
  25. Thelen K, Maier B, Faber M, Albrecht C, Fischer P, Pollerberg G. Translation of the cell adhesion molecule ALCAM in axonal growth cones - regulation and functional importance. J Cell Sci. 2012;125:1003-14 pubmed publisher
    ..In the present study, we show that ALCAM mRNA is present in axonal growth cones of RGCs in vivo and in vitro, and that translation of ALCAM occurs in RGC growth cones separated from their ..
  26. Wang P, Petralia R, Wang Y, Wenthold R, Brenowitz S. Functional NMDA receptors at axonal growth cones of young hippocampal neurons. J Neurosci. 2011;31:9289-97 pubmed publisher
    NMDA receptors (NMDARs) are critical to the development of the nervous system, although their roles at axonal growth cones are unclear. We examined NMDAR localization and function at axonal growth cones of young hippocampal neurons...
  27. Prokop A. The intricate relationship between microtubules and their associated motor proteins during axon growth and maintenance. Neural Dev. 2013;8:17 pubmed publisher
    ..this, MTs organize into parallel bundles that are established through extension at the leading axon tips within growth cones, and these bundles then form the architectural backbones, as well as the highways for axonal transport ..
  28. Marsick B, FLYNN K, Santiago Medina M, Bamburg J, Letourneau P. Activation of ADF/cofilin mediates attractive growth cone turning toward nerve growth factor and netrin-1. Dev Neurobiol. 2010;70:565-88 pubmed publisher
    Proper neural circuitry requires that growth cones, motile tips of extending axons, respond to molecular guidance cues expressed in the developing organism...
  29. Drinjakovic J, Jung H, Campbell D, Strochlic L, Dwivedy A, Holt C. E3 ligase Nedd4 promotes axon branching by downregulating PTEN. Neuron. 2010;65:341-57 pubmed publisher
    ..We identify Nedd4 as a prominently expressed E3 ligase in RGC axon growth cones and show that disrupting its function severely inhibits terminal branching...
  30. Shah S, Kang Y, Christensen B, Feng A, Kollmar R. Expression of Wnt receptors in adult spiral ganglion neurons: frizzled 9 localization at growth cones of regenerating neurites. Neuroscience. 2009;164:478-87 pubmed publisher
    ..Finally, frizzled 9 protein was found in the growth cones of adult spiral ganglion neurons that were regenerating neurites in culture...
  31. Norris A, Lundquist E. UNC-6/netrin and its receptors UNC-5 and UNC-40/DCC modulate growth cone protrusion in vivo in C. elegans. Development. 2011;138:4433-42 pubmed publisher
    ..Loss-of-function unc-5 mutants displayed increased protrusion in repelled growth cones, whereas loss-of-function unc-6 or unc-40 mutants caused decreased protrusion...
  32. Yu L, Zhou Y, Cheng S, Rao Y. Plexin a-semaphorin-1a reverse signaling regulates photoreceptor axon guidance in Drosophila. J Neurosci. 2010;30:12151-6 pubmed publisher
    ..Loss of PlexA, like loss of semala, disrupted the association of R-cell growth cones in the optic lobe...
  33. Suter D, Miller K. The emerging role of forces in axonal elongation. Prog Neurobiol. 2011;94:91-101 pubmed publisher
    ..However, recent work suggests that axons and growth cones also generate forces (through cytoskeletal dynamics, kinesin, dynein, and myosin), forces induce axonal ..
  34. Sergi P, Morana Roccasalvo I, Tonazzini I, Cecchini M, Micera S. Cell guidance on nanogratings: a computational model of the interplay between PC12 growth cones and nanostructures. PLoS ONE. 2013;8:e70304 pubmed publisher
    ..simulations were used to qualitatively assess the distribution of stresses at the interface between non-spread growth cones and filopodia, and to study their dependence on filopodial length and orientation...
  35. Colak D, Ji S, Porse B, Jaffrey S. Regulation of axon guidance by compartmentalized nonsense-mediated mRNA decay. Cell. 2013;153:1252-65 pubmed publisher
    b>Growth cones enable axons to navigate toward their targets by responding to extracellular signaling molecules. Growth-cone responses are mediated in part by the local translation of axonal messenger RNAs (mRNAs)...
  36. Tahirovic S, Hellal F, Neukirchen D, Hindges R, Garvalov B, FLYNN K, et al. Rac1 regulates neuronal polarization through the WAVE complex. J Neurosci. 2010;30:6930-43 pubmed publisher
    ..In addition, Rac1 ablation disrupts lamellipodia formation in growth cones. The analysis of Rac1 effectors revealed the absence of the Wiskott-Aldrich syndrome protein (WASP) family ..
  37. Hoffman Kim D, Mitchel J, Bellamkonda R. Topography, cell response, and nerve regeneration. Annu Rev Biomed Eng. 2010;12:203-31 pubmed publisher
    ..Studies reviewed here include those of topography on cellular organization and function as well as potential cellular mechanisms of response. ..
  38. Sato Y, Mita S, Fukushima N, Fujisawa H, Saga Y, Hirata T. Induction of axon growth arrest without growth cone collapse through the N-terminal region of four-transmembrane glycoprotein M6a. Dev Neurobiol. 2011;71:733-46 pubmed publisher
    ..In general, rapid axon growth is correlated with active growth cones driven by dynamic actin filaments...
  39. Schwabe T, Neuert H, Clandinin T. A network of cadherin-mediated interactions polarizes growth cones to determine targeting specificity. Cell. 2013;154:351-64 pubmed publisher
    Neuronal growth cones select synaptic partners through interactions with multiple cell surfaces in their environment...
  40. Kerstein P, Jacques Fricke B, Rengifo J, Mogen B, Williams J, Gottlieb P, et al. Mechanosensitive TRPC1 channels promote calpain proteolysis of talin to regulate spinal axon outgrowth. J Neurosci. 2013;33:273-85 pubmed publisher
    ..receptor potential canonical 1 (TRPC1) subunits assemble mechanosensitive (MS) channels on Xenopus neuronal growth cones that regulate the extension and direction of axon outgrowth on rigid, but not compliant, substrata...
  41. Norris A, Dyer J, Lundquist E. The Arp2/3 complex, UNC-115/abLIM, and UNC-34/Enabled regulate axon guidance and growth cone filopodia formation in Caenorhabditis elegans. Neural Dev. 2009;4:38 pubmed publisher
    ..Analysis of developing growth cones in vivo showed that arx mutants displayed defects in filopodia and reduced growth cone size...
  42. Craig E, Van Goor D, Forscher P, Mogilner A. Membrane tension, myosin force, and actin turnover maintain actin treadmill in the nerve growth cone. Biophys J. 2012;102:1503-13 pubmed publisher
    ..We estimate forces in the actin treadmill, and we demonstrate that measured G-actin distributions are consistent with the existence of a forward-directed fluid flow that transports G-actin to the leading edge. ..
  43. Sasaki Y, Welshhans K, Wen Z, Yao J, Xu M, Goshima Y, et al. Phosphorylation of zipcode binding protein 1 is required for brain-derived neurotrophic factor signaling of local beta-actin synthesis and growth cone turning. J Neurosci. 2010;30:9349-58 pubmed publisher
    The localization of specific mRNAs and their local translation in growth cones of developing axons has been shown to play an important mechanism to regulate growth cone turning responses to attractive or repulsive cues...
  44. Neukirchen D, Bradke F. Cytoplasmic linker proteins regulate neuronal polarization through microtubule and growth cone dynamics. J Neurosci. 2011;31:1528-38 pubmed publisher
    ..Together, our data suggest that CLIPs enable neuronal polarization by controlling the stabilization of microtubules and growth cone dynamics. ..
  45. Van Goor D, Hyland C, Schaefer A, Forscher P. The role of actin turnover in retrograde actin network flow in neuronal growth cones. PLoS ONE. 2012;7:e30959 pubmed publisher
    ..of actin filament polymerization and depolymerization maintains a steady state network treadmill in neuronal growth cones essential for motility and guidance...
  46. Gonçalves Pimentel C, Gombos R, Mihály J, Sánchez Soriano N, Prokop A. Dissecting regulatory networks of filopodia formation in a Drosophila growth cone model. PLoS ONE. 2011;6:e18340 pubmed publisher
    ..Our genetic data support a model in which Arp2/3 and DAAM cooperate in a common mechanism of filopodia formation that essentially depends on enabled, and is regulated through profilin activity at different steps. ..
  47. Tojima T. Intracellular signaling and membrane trafficking control bidirectional growth cone guidance. Neurosci Res. 2012;73:269-74 pubmed publisher
    The formation of precise neuronal networks is critically dependent on the motility of axonal growth cones. Extracellular gradients of guidance cues evoke localized Ca(2+) elevations to attract or repel the growth cone...
  48. Mitchell C, Gasperini R, Small D, Foa L. STIM1 is necessary for store-operated calcium entry in turning growth cones. J Neurochem. 2012;122:1155-66 pubmed publisher
    ..the mechanisms that regulate calcium signalling, particularly the regulation of internal calcium stores within growth cones, are yet to be fully determined...
  49. Myers J, Gomez T. Focal adhesion kinase promotes integrin adhesion dynamics necessary for chemotropic turning of nerve growth cones. J Neurosci. 2011;31:13585-95 pubmed publisher
    ..repulsive growth factors, but little is known about the effectors or cellular mechanisms that FAK controls in growth cones on ECM proteins...
  50. Jean D, Baas P, Black M. A novel role for doublecortin and doublecortin-like kinase in regulating growth cone microtubules. Hum Mol Genet. 2012;21:5511-27 pubmed publisher
    ..These findings support a role for DCX and DCLK in enabling microtubules to overcome retrograde actin-based forces, thereby facilitating the ability of the growth cone to carry out its crucial path-finding functions. ..
  51. Marin O, Valiente M, Ge X, Tsai L. Guiding neuronal cell migrations. Cold Spring Harb Perspect Biol. 2010;2:a001834 pubmed publisher
    ..Perhaps more surprisingly, the cellular mechanisms underlying the response of the leading process of migrating cells to guidance cues might be different to those involved in growth cone steering, at least for some neuronal populations. ..
  52. Kabayama H, Takeuchi M, Taniguchi M, Tokushige N, Kozaki S, Mizutani A, et al. Syntaxin 1B suppresses macropinocytosis and semaphorin 3A-induced growth cone collapse. J Neurosci. 2011;31:7357-64 pubmed publisher
    ..We have reported previously that macropinocytosis is induced in growth cones of chick dorsal root ganglion neurons by semaphorin 3A (Sema3A), a repulsive axon guidance cue, and that Sema3A-..
  53. Koch D, Rosoff W, Jiang J, Geller H, Urbach J. Strength in the periphery: growth cone biomechanics and substrate rigidity response in peripheral and central nervous system neurons. Biophys J. 2012;102:452-60 pubmed publisher
    ..force microscopy, we also find a substantial difference in growth cone traction force generation, with DRG growth cones exerting severalfold larger forces compared with hippocampal growth cones...