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Transient cell–cell interactions in neural circuit formation

Nature Reviews Neuroscience volume 10, pages 262–271 (2009)Cite this article

Key Points

  • Transient cell–cell interactions involving presynaptic neurons and cells that are extrinsic to the neural circuit have important roles in the assembly of the nervous system. In contrast to classically described environmental axon guidance cues, which attract or repel axons over long distances, these cell–cell interactions transiently mark a specific spatial coordinate and delineate choice points for axon growth or synaptogenesis.

  • These cell–cell interactions have diverse roles in patterning neuronal connectivity, including roles as intermediate targets in axon guidance, scaffolds for axonal growth, transient synaptic targets and guideposts for synapse target selection. Examples of these cell–cell interactions are found in many different organisms and diverse cellular contexts.

  • Many of the cells involved in transient cell–cell interactions have multiple roles in the development of the nervous system, including specification of neural precursors, neuronal migration and axon arborization.

  • The molecular mechanisms that underlie these transient cell–cell interactions include secretion of short-range attractive and repulsive cues, expression of cell surface adhesion molecules and secretion of long-range signals that pattern synaptic connectivity.

Abstract

The wiring of the nervous system requires a complex orchestration of developmental events. Emerging evidence suggests that transient cell–cell interactions often serve as positional cues for axon guidance and synaptogenesis during the assembly of neural circuits. In contrast to the relatively stable cellular interactions between synaptic partners in mature circuits, these transient interactions involve cells that are not destined to be pre- or postsynaptic cells. Here we review the roles of these transient cell–cell interactions in a variety of developmental contexts and describe the mechanisms through which they organize neural connections.

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Figure 1: Conceptual roles for transient cell–cell interactions in neural circuit formation.
Figure 2: Guidepost cells in grasshopper pioneer neuron axon guidance.
Figure 3: The floor plate as an intermediate target in axon guidance.
Figure 4: Radial glia and CD44+ cells in retinal axon guidance.
Figure 5: Bergmann glia direct stellate interneuron arborization onto Purkinje cell dendrites.
Figure 6: The role of Cajal–Retzius cells and subplate cells in neural circuit formation.
Figure 7: Non-neuronal cells as guideposts in synaptic specificity.

References

  1. Bate, C. M. Pioneer neurones in an insect embryo. Nature 260, 54–56 (1976).

    Article  CAS  PubMed  Google Scholar 

  2. Caudy, M. & Bentley, D. Pioneer growth cone steering along a series of neuronal and non-neuronal cues of different affinities. J. Neurosci. 6, 1781–1795 (1986).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Bentley, D. & Keshishian, H. Pathfinding by peripheral pioneer neurons in grasshoppers. Science 218, 1082–1088 (1982).

    Article  CAS  PubMed  Google Scholar 

  4. Bentley, D. & Caudy, M. Pioneer axons lose directed growth after selective killing of guidepost cells. Nature 304, 62–65 (1983). The first demonstration that guidepost cells play a part in axon guidance.

    Article  CAS  PubMed  Google Scholar 

  5. Klambt, C., Jacobs, J. R. & Goodman, C. S. The midline of the Drosophila central nervous system: a model for the genetic analysis of cell fate, cell migration, and growth cone guidance. Cell 64, 801–815 (1991).

    Article  CAS  PubMed  Google Scholar 

  6. Bovolenta, P. & Dodd, J. Perturbation of neuronal differentiation and axon guidance in the spinal cord of mouse embryos lacking a floor plate: analysis of Danforth's short-tail mutation. Development 113, 625–639 (1991).

    CAS  PubMed  Google Scholar 

  7. Bernhardt, R. R., Nguyen, N. & Kuwada, J. Y. Growth cone guidance by floor plate cells in the spinal cord of zebrafish embryos. Neuron 8, 869–882 (1992).

    Article  CAS  PubMed  Google Scholar 

  8. Greenspoon, S., Patel, C. K., Hashmi, S., Bernhardt, R. R. & Kuwada, J. Y. The notochord and floor plate guide growth cones in the zebrafish spinal cord. J. Neurosci. 15, 5956–5965 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Hatta, K. Role of the floor plate in axonal patterning in the zebrafish CNS. Neuron 9, 629–642 (1992).

    Article  CAS  PubMed  Google Scholar 

  10. Kadison, S. R., Murakami, F., Matise, M. P. & Kaprielian, Z. The role of floor plate contact in the elaboration of contralateral commissural projections within the embryonic mouse spinal cord. Dev. Biol. 296, 499–513 (2006).

    Article  CAS  PubMed  Google Scholar 

  11. Serafini, T. et al. Netrin-1 is required for commissural axon guidance in the developing vertebrate nervous system. Cell 87, 1001–1014 (1996).

    CAS  PubMed  Google Scholar 

  12. Tessier-Lavigne, M. & Goodman, C. S. The molecular biology of axon guidance. Science 274, 1123–1133 (1996).

    Article  CAS  PubMed  Google Scholar 

  13. Charron, F., Stein, E., Jeong, J., McMahon, A. P. & Tessier-Lavigne, M. The morphogen sonic hedgehog is an axonal chemoattractant that collaborates with netrin-1 in midline axon guidance. Cell 113, 11–23 (2003).

    Article  CAS  PubMed  Google Scholar 

  14. Okada, A. et al. Boc is a receptor for sonic hedgehog in the guidance of commissural axons. Nature 444, 369–373 (2006).

    Article  CAS  PubMed  Google Scholar 

  15. Stoeckli, E. T., Sonderegger, P., Pollerberg, G. E. & Landmesser, L. T. Interference with axonin-1 and NrCAM interactions unmasks a floor-plate activity inhibitory for commissural axons. Neuron 18, 209–221 (1997).

    Article  CAS  PubMed  Google Scholar 

  16. Stoeckli, E. T. & Landmesser, L. T. Axonin-1, Nr-CAM, and Ng-CAM play different roles in the in vivo guidance of chick commissural neurons. Neuron 14, 1165–1179 (1995).

    Article  CAS  PubMed  Google Scholar 

  17. Rothberg, J. M., Jacobs, J. R., Goodman, C. S. & Artavanis-Tsakonas, S. slit: an extracellular protein necessary for development of midline glia and commissural axon pathways contains both EGF and LRR domains. Genes Dev. 4, 2169–2187 (1990).

    Article  CAS  PubMed  Google Scholar 

  18. Kidd, T. et al. Roundabout controls axon crossing of the CNS midline and defines a novel subfamily of evolutionarily conserved guidance receptors. Cell 92, 205–215 (1998).

    Article  CAS  PubMed  Google Scholar 

  19. Kidd, T., Bland, K. S. & Goodman, C. S. Slit is the midline repellent for the robo receptor in Drosophila. Cell 96, 785–794 (1999).

    Article  CAS  PubMed  Google Scholar 

  20. Long, H. et al. Conserved roles for Slit and Robo proteins in midline commissural axon guidance. Neuron 42, 213–223 (2004).

    Article  CAS  PubMed  Google Scholar 

  21. Keleman, K. et al. Comm sorts robo to control axon guidance at the Drosophila midline. Cell 110, 415–427 (2002).

    Article  CAS  PubMed  Google Scholar 

  22. Keleman, K., Ribeiro, C. & Dickson, B. J. Comm function in commissural axon guidance: cell-autonomous sorting of Robo in vivo. Nature Neurosci. 8, 156–163 (2005).

    Article  CAS  PubMed  Google Scholar 

  23. Kidd, T., Russell, C., Goodman, C. S. & Tear, G. Dosage-sensitive and complementary functions of roundabout and commissureless control axon crossing of the CNS midline. Neuron 20, 25–33 (1998).

    Article  CAS  PubMed  Google Scholar 

  24. Myat, A. et al. Drosophila Nedd4, a ubiquitin ligase, is recruited by Commissureless to control cell surface levels of the roundabout receptor. Neuron 35, 447–459 (2002).

    Article  CAS  PubMed  Google Scholar 

  25. Sabatier, C. et al. The divergent Robo family protein rig-1/Robo3 is a negative regulator of slit responsiveness required for midline crossing by commissural axons. Cell 117, 157–169 (2004).

    Article  CAS  PubMed  Google Scholar 

  26. Chen, Z., Gore, B. B., Long, H., Ma, L. & Tessier-Lavigne, M. Alternative splicing of the Robo3 axon guidance receptor governs the midline switch from attraction to repulsion. Neuron 58, 325–332 (2008).

    Article  CAS  PubMed  Google Scholar 

  27. Stein, E. & Tessier-Lavigne, M. Hierarchical organization of guidance receptors: silencing of netrin attraction by slit through a Robo/DCC receptor complex. Science 291, 1928–1938 (2001). This study demonstrated that netrin attraction can be silenced through an interaction between the Slit receptors the Robos and the netrin receptor, DCC.

    Article  CAS  PubMed  Google Scholar 

  28. Wang, H. & Tessier-Lavigne, M. En passant neurotrophic action of an intermediate axonal target in the developing mammalian CNS. Nature 401, 765–769 (1999).

    Article  CAS  PubMed  Google Scholar 

  29. Sretavan, D. W., Feng, L., Pure, E. & Reichardt, L. F. Embryonic neurons of the developing optic chiasm express L1 and CD44, cell surface molecules with opposing effects on retinal axon growth. Neuron 12, 957–975 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Wilson, S. W., Ross, L. S., Parrett, T. & Easter, S. S. Jr. The development of a simple scaffold of axon tracts in the brain of the embryonic zebrafish, Brachydanio rerio. Development 108, 121–145 (1990).

    CAS  PubMed  Google Scholar 

  31. Sretavan, D. W., Pure, E., Siegel, M. W. & Reichardt, L. F. Disruption of retinal axon ingrowth by ablation of embryonic mouse optic chiasm neurons. Science 269, 98–101 (1995). In this study, ablation of CD44+ cells at the optic chiasm prevented the growth of RGC axons from the contralateral side, implicating CD44+ cells as guideposts in the formation of the optic chiasm.

    Article  CAS  PubMed  Google Scholar 

  32. Marcus, R. C., Blazeski, R., Godement, P. & Mason, C. A. Retinal axon divergence in the optic chiasm: uncrossed axons diverge from crossed axons within a midline glial specialization. J. Neurosci. 15, 3716–3729 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Williams, S. E. et al. Ephrin-B2 and EphB1 mediate retinal axon divergence at the optic chiasm. Neuron 39, 919–935 (2003). This paper showed that EphB2–EPHB1 interactions between radial glia and RGC axons are required for the formation of the RGC ipsilateral projection.

    Article  CAS  PubMed  Google Scholar 

  34. Shu, T. & Richards, L. J. Cortical axon guidance by the glial wedge during the development of the corpus callosum. J. Neurosci. 21, 2749–2758 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Jellies, J. & Kristan, W. B. Jr. An identified cell is required for the formation of a major nerve during embryogenesis in the leech. J. Neurobiol. 19, 153–165 (1988).

    Article  CAS  PubMed  Google Scholar 

  36. Carr, J. N. & Taghert, P. H. Formation of the transverse nerve in moth embryos. II. Stereotyped growth by the axons of identified neuroendocrine neurons. Dev. Biol. 130, 500–512 (1988).

    Article  CAS  PubMed  Google Scholar 

  37. Carr, J. N. & Taghert, P. H. Formation of the transverse nerve in moth embryos. I. A scaffold of nonneuronal cells prefigures the nerve. Dev. Biol. 130, 487–499 (1988).

    Article  CAS  PubMed  Google Scholar 

  38. Sato, Y., Hirata, T., Ogawa, M. & Fujisawa, H. Requirement for early-generated neurons recognized by monoclonal antibody lot1 in the formation of lateral olfactory tract. J. Neurosci. 18, 7800–7810 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Lopez-Bendito, G. et al. Tangential neuronal migration controls axon guidance: a role for neuregulin-1 in thalamocortical axon navigation. Cell 125, 127–142 (2006). This study demonstrated that corridor cells act as a permissive bridge for dorsal thalamic axons to grow through the internal capsule.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Ango, F. et al. Bergmann glia and the recognition molecule CHL1 organize GABAergic axons and direct innervation of Purkinje cell dendrites. PLoS Biol. 6, e103 (2008). This study demonstrated that Bergmann glia have essential roles in mediating stellate axon arborization and synapse formation onto Purkinje cell dendrites.

    Google Scholar 

  41. Sanes, J. R. & Yamagata, M. Formation of lamina-specific synaptic connections. Curr. Opin. Neurobiol. 9, 79–87 (1999).

    Article  CAS  PubMed  Google Scholar 

  42. Soriano, E., Del Rio, J. A., Martinez, A. & Super, H. Organization of the embryonic and early postnatal murine hippocampus. I. Immunocytochemical characterization of neuronal populations in the subplate and marginal zone. J. Comp. Neurol. 342, 571–595 (1994).

    Article  CAS  PubMed  Google Scholar 

  43. Super, H., Martinez, A., Del Rio, J. A. & Soriano, E. Involvement of distinct pioneer neurons in the formation of layer-specific connections in the hippocampus. J. Neurosci. 18, 4616–4626 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Super, H. & Soriano, E. The organization of the embryonic and early postnatal murine hippocampus. II. Development of entorhinal, commissural, and septal connections studied with the lipophilic tracer DiI. J. Comp. Neurol. 344, 101–120 (1994).

    Article  CAS  PubMed  Google Scholar 

  45. Del Rio, J. A. et al. A role for Cajal-Retzius cells and reelin in the development of hippocampal connections. Nature 385, 70–74 (1997). This study showed that ablation of Cajal–Retzius cells prevents layer-specific innervation of hippocampal axons.

    Article  CAS  PubMed  Google Scholar 

  46. Allendoerfer, K. L. & Shatz, C. J. The subplate, a transient neocortical structure: its role in the development of connections between thalamus and cortex. Annu. Rev. Neurosci. 17, 185–218 (1994).

    Article  CAS  PubMed  Google Scholar 

  47. Kanold, P. O. Transient microcircuits formed by subplate neurons and their role in functional development of thalamocortical connections. Neuroreport 15, 2149–2153 (2004).

    Article  PubMed  Google Scholar 

  48. Ghosh, A., Antonini, A., McConnell, S. K. & Shatz, C. J. Requirement for subplate neurons in the formation of thalamocortical connections. Nature 347, 179–181 (1990).

    Article  CAS  PubMed  Google Scholar 

  49. Ghosh, A. & Shatz, C. J. Involvement of subplate neurons in the formation of ocular dominance columns. Science 255, 1441–1443 (1992).

    Article  CAS  PubMed  Google Scholar 

  50. Kanold, P. O., Kara, P., Reid, R. C. & Shatz, C. J. Role of subplate neurons in functional maturation of visual cortical columns. Science 301, 521–525 (2003).

    Article  CAS  PubMed  Google Scholar 

  51. Kanold, P. O. & Shatz, C. J. Subplate neurons regulate maturation of cortical inhibition and outcome of ocular dominance plasticity. Neuron 51, 627–638 (2006).

    Article  CAS  PubMed  Google Scholar 

  52. Colon-Ramos, D. A., Margeta, M. A. & Shen, K. Glia promote local synaptogenesis through UNC-6 (netrin) signaling in C. elegans. Science 318, 103–106 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Yoshimura, S., Murray, J. I., Lu, Y., Waterston, R. H. & Shaham, S. mls-2 and vab-3 control glia development, hlh-17/Olig expression and glia-dependent neurite extension in C. elegans. Development 135, 2263–2275 (2008).

    Article  CAS  PubMed  Google Scholar 

  54. Shen, K. & Bargmann, C. I. The immunoglobulin superfamily protein SYG-1 determines the location of specific synapses in C. elegans. Cell 112, 619–630 (2003). This study, along with reference 55, revealed that HSNL synapse formation is regulated by contact-mediated cues that pass between vulval epithelial cells and the presynaptic HSNL neuron.

    Article  CAS  PubMed  Google Scholar 

  55. Shen, K., Fetter, R. D. & Bargmann, C. I. Synaptic specificity is generated by the synaptic guidepost protein SYG-2 and its receptor, SYG-1. Cell 116, 869–881 (2004).

    Article  CAS  PubMed  Google Scholar 

  56. Li, C. & Chalfie, M. Organogenesis in C. elegans: positioning of neurons and muscles in the egg-laying system. Neuron 4, 681–695 (1990).

    Article  CAS  PubMed  Google Scholar 

  57. Klassen, M. P. & Shen, K. Wnt signaling positions neuromuscular connectivity by inhibiting synapse formation in C. elegans. Cell 130, 704–716 (2007). This study, along with reference 58, demonstrated that long-range cues can inhibit synaptogenesis in subcellular regions of the axon.

    Article  CAS  PubMed  Google Scholar 

  58. Poon, V. Y., Klassen, M. P. & Shen, K. UNC-6/netrin and its receptor UNC-5 locally exclude presynaptic components from dendrites. Nature 455, 669–673 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. McQuillen, P. S., Sheldon, R. A., Shatz, C. J. & Ferriero, D. M. Selective vulnerability of subplate neurons after early neonatal hypoxia-ischemia. J. Neurosci. 23, 3308–3315 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Cioni, G. et al. Cerebral visual impairment in preterm infants with periventricular leukomalacia. Pediatr. Neurol. 17, 331–338 (1997).

    Article  CAS  PubMed  Google Scholar 

  61. Lanzi, G. et al. Cerebral visual impairment in periventricular leukomalacia. Neuropediatrics 29, 145–150 (1998).

    Article  CAS  PubMed  Google Scholar 

  62. McQuillen, P. S. & Ferriero, D. M. Selective vulnerability in the developing central nervous system. Pediatr. Neurol. 30, 227–235 (2004).

    Article  PubMed  Google Scholar 

  63. Maalouf, E. F. et al. Comparison of findings on cranial ultrasound and magnetic resonance imaging in preterm infants. Pediatrics 107, 719–727 (2001).

    Article  CAS  PubMed  Google Scholar 

  64. McQuillen, P. S. & Ferriero, D. M. Perinatal subplate neuron injury: implications for cortical development and plasticity. Brain Pathol. 15, 250–260 (2005).

    Article  CAS  PubMed  Google Scholar 

  65. Blumcke, I., Thom, M. & Wiestler, O. D. Ammon's horn sclerosis: a maldevelopmental disorder associated with temporal lobe epilepsy. Brain Pathol. 12, 199–211 (2002).

    PubMed  Google Scholar 

  66. Fatemi, S. H. Reelin glycoprotein: structure, biology and roles in health and disease. Mol. Psychiatry 10, 251–257 (2005).

    Article  CAS  PubMed  Google Scholar 

  67. Fatemi, S. H., Earle, J. A. & McMenomy, T. Reduction in Reelin immunoreactivity in hippocampus of subjects with schizophrenia, bipolar disorder and major depression. Mol. Psychiatry 5, 654–663, 571 (2000).

    Article  CAS  PubMed  Google Scholar 

  68. Fatemi, S. H., Stary, J. M. & Egan, E. A. Reduced blood levels of reelin as a vulnerability factor in pathophysiology of autistic disorder. Cell. Mol. Neurobiol. 22, 139–152 (2002).

    Article  CAS  PubMed  Google Scholar 

  69. Impagnatiello, F. et al. A decrease of reelin expression as a putative vulnerability factor in schizophrenia. Proc. Natl Acad. Sci. USA 95, 15718–15723 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Ingham, P. W. & McMahon, A. P. Hedgehog signaling in animal development: paradigms and principles. Genes Dev. 15, 3059–3087 (2001).

    Article  CAS  PubMed  Google Scholar 

  71. Jessell, T. M. Neuronal specification in the spinal cord: inductive signals and transcriptional codes. Nature Rev. Genet. 1, 20–29 (2000).

    Article  CAS  PubMed  Google Scholar 

  72. Marti, E. & Bovolenta, P. Sonic hedgehog in CNS development: one signal, multiple outputs. Trends Neurosci. 25, 89–96 (2002).

    Article  CAS  PubMed  Google Scholar 

  73. Frotscher, M. Cajal-Retzius cells, Reelin, and the formation of layers. Curr. Opin. Neurobiol. 8, 570–575 (1998).

    Article  CAS  PubMed  Google Scholar 

  74. Soriano, E. & Del Rio, J. A. The cells of Cajal-Retzius: still a mystery one century after. Neuron 46, 389–394 (2005).

    Article  CAS  PubMed  Google Scholar 

  75. Garriga, G., Desai, C. & Horvitz, H. R. Cell interactions control the direction of outgrowth, branching and fasciculation of the HSN axons of Caenorhabditis elegans. Development 117, 1071–1087 (1993).

    CAS  PubMed  Google Scholar 

  76. Margeta, M. A., Shen, K. & Grill, B. Building a synapse: lessons on synaptic specificity and presynaptic assembly from the nematode C. elegans. Curr. Opin. Neurobiol. 18, 69–76 (2008).

    Article  CAS  PubMed  Google Scholar 

  77. Del Rio, J. A. et al. Differential survival of Cajal-Retzius cells in organotypic cultures of hippocampus and neocortex. J. Neurosci. 16, 6896–6907 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Petros, T. J., Rebsam, A. & Mason, C. A. Retinal axon growth at the optic chiasm: to cross or not to cross. Annu. Rev. Neurosci. 31, 295–315 (2008).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank members of K.S.'s laboratory for helpful discussions, M. Margeta for reading of the manuscript and the reviewers for their helpful suggestions. We apologize to authors whose work we were unable to include owing to space constraints.

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Authors and Affiliations

  1. Neurosciences Program, Stanford University, Stanford, 94305, California, USA

    Daniel L. Chao & Kang Shen

  2. Department of Biology, Howard Hughes Medical Institute, 385 Serra Mall, Stanford University, Stanford, 94305, California, USA

    Daniel L. Chao & Kang Shen

  3. Department of Cell and Neurobiology, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, 1501 San Pablo Street, Los Angeles, 90089, California, USA

    Le Ma

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Glossary

En passant synapses

Synapses formed along the shaft of the axon, in contrast to terminal synapses, which are formed only at the end of the axon.

Pioneer axon

An axon that develops early in a fascicle and acts as a scaffold for later-developing neurons to grow on.

Floor plate

Specialized neural epithelial cells found at the ventral midline of the spinal cord that secrete various factors involved in organizing the nervous system.

Netrins

Secreted proteins similar to laminin that were first discovered through their involvement in axon guidance.

Slits

Axon guidance factors that were first discovered through their roles as chemorepellents.

Optic chiasm

The anatomical landmark where retinal ganglion cell axons from both eyes converge and cross.

Radial glia

Cells with astrocytic characteristics and processes that span the region from the lumen of the ventricle to the pial surface. They have multiple roles during neural development.

Mitral cell

The main efferent output of the olfactory bulb.

Bergmann glial cell

An astrocyte that extends long radial fibres throughout the entire cerebellum.

Entorhinal cortex

The brain region that provides the main input to the hippocampus.

Reelin

A secreted glycoprotein that is implicated in neuronal migration and other signalling pathways.

Cajal–Retzius cell

One of the earliest-born classes of neurons. They are located along the surface of the entire cortex during most of cortical development.

Lateral geniculate nucleus

The area of the thalamus that receives projections from the retina and sends projections to the visual cortex.

Subplate

A transient cell layer located below the cortical plate early in development that is important for establishing thalamocortical projections.

Wnts

A family of well-conserved secreted molecules that have multiple roles in cell–cell interactions.

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Chao, D., Ma, L. & Shen, K. Transient cell–cell interactions in neural circuit formation. Nat Rev Neurosci 10, 262–271 (2009). https://doi.org/10.1038/nrn2594

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