Genetics and Cell Biology of Building Specific Synaptic Connectivity

Overview

Journal Annu Rev Neurosci

Specialty Neurology

Date 2010 Apr 7

PMID 20367446

Citations 134

Authors

Kang Shen

Peter Scheiffele

Affiliations

Soon will be listed here.

Abstract

The assembly of specific synaptic connections during development of the nervous system represents a remarkable example of cellular recognition and differentiation. Neurons employ several different cellular signaling strategies to solve this puzzle, which successively limit unwanted interactions and reduce the number of direct recognition events that are required to result in a specific connectivity pattern. Specificity mechanisms include the action of contact-mediated and long-range signals that support or inhibit synapse formation, which can take place directly between synaptic partners or with transient partners and transient cell populations. The molecular signals that drive the synaptic differentiation process at individual synapses in the central nervous system are similarly diverse and act through multiple, parallel differentiation pathways. This molecular complexity balances the need for central circuits to be assembled with high accuracy during development while retaining plasticity for local and dynamic regulation.

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References

Hall A, LUCAS F, Salinas P . Axonal remodeling and synaptic differentiation in the cerebellum is regulated by WNT-7a signaling. Cell. 2000; 100(5):525-35. DOI: 10.1016/s0092-8674(00)80689-3. View

Ghosh A, Shatz C . Involvement of subplate neurons in the formation of ocular dominance columns. Science. 1992; 255(5050):1441-3. DOI: 10.1126/science.1542795. View

Korkut C, Budnik V . WNTs tune up the neuromuscular junction. Nat Rev Neurosci. 2009; 10(9):627-34. PMC: 3499984. DOI: 10.1038/nrn2681. View

Wadsworth W, Bhatt H, Hedgecock E . Neuroglia and pioneer neurons express UNC-6 to provide global and local netrin cues for guiding migrations in C. elegans. Neuron. 1996; 16(1):35-46. DOI: 10.1016/s0896-6273(00)80021-5. View

Li J, Ashley J, Budnik V, Bhat M . Crucial role of Drosophila neurexin in proper active zone apposition to postsynaptic densities, synaptic growth, and synaptic transmission. Neuron. 2007; 55(5):741-55. PMC: 2039911. DOI: 10.1016/j.neuron.2007.08.002. View

Sia G, Beique J, Rumbaugh G, Cho R, Worley P, Huganir R . Interaction of the N-terminal domain of the AMPA receptor GluR4 subunit with the neuronal pentraxin NP1 mediates GluR4 synaptic recruitment. Neuron. 2007; 55(1):87-102. DOI: 10.1016/j.neuron.2007.06.020. View

Biederer T, Sara Y, Mozhayeva M, Atasoy D, Liu X, Kavalali E . SynCAM, a synaptic adhesion molecule that drives synapse assembly. Science. 2002; 297(5586):1525-31. DOI: 10.1126/science.1072356. View

Marques G, Bao H, Haerry T, Shimell M, Duchek P, Zhang B . The Drosophila BMP type II receptor Wishful Thinking regulates neuromuscular synapse morphology and function. Neuron. 2002; 33(4):529-43. DOI: 10.1016/s0896-6273(02)00595-0. View

Ango F, Di Cristo G, Higashiyama H, Bennett V, Wu P, Huang Z . Ankyrin-based subcellular gradient of neurofascin, an immunoglobulin family protein, directs GABAergic innervation at purkinje axon initial segment. Cell. 2004; 119(2):257-72. DOI: 10.1016/j.cell.2004.10.004. View

10.

Ataman B, Ashley J, Gorczyca M, Ramachandran P, Fouquet W, Sigrist S . Rapid activity-dependent modifications in synaptic structure and function require bidirectional Wnt signaling. Neuron. 2008; 57(5):705-18. PMC: 2435264. DOI: 10.1016/j.neuron.2008.01.026. View

11.

Hallam S, Jin Y . lin-14 regulates the timing of synaptic remodelling in Caenorhabditis elegans. Nature. 1998; 395(6697):78-82. DOI: 10.1038/25757. View

12.

Esumi S, Kakazu N, Taguchi Y, Hirayama T, Sasaki A, Hirabayashi T . Monoallelic yet combinatorial expression of variable exons of the protocadherin-alpha gene cluster in single neurons. Nat Genet. 2005; 37(2):171-6. DOI: 10.1038/ng1500. View

13.

Nitkin R, Smith M, Magill C, Fallon J, Yao Y, Wallace B . Identification of agrin, a synaptic organizing protein from Torpedo electric organ. J Cell Biol. 1987; 105(6 Pt 1):2471-8. PMC: 2114709. DOI: 10.1083/jcb.105.6.2471. View

14.

Patton B, Miner J, Chiu A, Sanes J . Distribution and function of laminins in the neuromuscular system of developing, adult, and mutant mice. J Cell Biol. 1998; 139(6):1507-21. PMC: 2132624. DOI: 10.1083/jcb.139.6.1507. View

15.

Fernandez-Monreal M, Kang S, Phillips G . Gamma-protocadherin homophilic interaction and intracellular trafficking is controlled by the cytoplasmic domain in neurons. Mol Cell Neurosci. 2009; 40(3):344-53. PMC: 2646808. DOI: 10.1016/j.mcn.2008.12.002. View

16.

Aberle H, Pejmun Haghighi A, Fetter R, McCabe B, Magalhaes T, Goodman C . wishful thinking encodes a BMP type II receptor that regulates synaptic growth in Drosophila. Neuron. 2002; 33(4):545-58. DOI: 10.1016/s0896-6273(02)00589-5. View

17.

Morishita H, Yagi T . Protocadherin family: diversity, structure, and function. Curr Opin Cell Biol. 2007; 19(5):584-92. DOI: 10.1016/j.ceb.2007.09.006. View

18.

Mauch D, Nagler K, Schumacher S, Goritz C, Muller E, Otto A . CNS synaptogenesis promoted by glia-derived cholesterol. Science. 2001; 294(5545):1354-7. DOI: 10.1126/science.294.5545.1354. View

19.

Zhang B, Luo S, Wang Q, Suzuki T, Xiong W, Mei L . LRP4 serves as a coreceptor of agrin. Neuron. 2008; 60(2):285-97. PMC: 2743173. DOI: 10.1016/j.neuron.2008.10.006. View

20.

Ghosh A, Antonini A, McConnell S, Shatz C . Requirement for subplate neurons in the formation of thalamocortical connections. Nature. 1990; 347(6289):179-81. DOI: 10.1038/347179a0. View