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Intercellular communication that mediates formation of the neuromuscular junction

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Abstract

Reciprocal signals between the motor axon and myofiber induce structural and functional differentiation in the developing neuromuscular junction (NMJ). Elevation of presynaptic acetylcholine (ACh) release on nerve-muscle contact and the correlated increase in axonal-free calcium are triggered by unidentified membrane molecules. Restriction of axon growth to the developing NMJ and formation of active zones for ACh release in the presynaptic terminal may be induced by molecules in the synaptic basal lamina, such as S-laminin, heparin binding growth factors, and agrin. Acetylcholine receptor (AChR) synthesis by muscle cells may be increased by calcitonin gene-related peptide (CGRP), ascorbic acid, and AChR-inducing activity (ARIA)/heregulin, which is the best-established regulator. Heparin binding growth factors, proteases, adhesion molecules, and agrin all may be involved in the induction of AChR redistribution to form postsynaptic-like aggregates. However, the strongest case has been made for agrin's involvement. “Knockout” experiments have implicated agrin as a primary anterograde signal for postsynaptic differentiation and muscle-specific kinase (MuSK), as a putative agrin receptor. It is likely that both presynaptic and postsynaptic differentiation are induced by multiple molecular signals. Future research should reveal the physiological roles of different molecules, their interactions, and the identity of other molecular participants.

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References

  • Allen F. and Warner A. (1991) Gap junctional communication during neuromuscular junction formation.Neuron 6, 101–111.

    Article  PubMed  CAS  Google Scholar 

  • Altiok N., Bessereau J. L. and Changeux J. P. (1995) ErbB3 and ErbB2/neu mediate the effect of heregulin on acetylcholine receptor gene expression in muscle: differential expression at the endplate.EMBO J. 14, 4258–4266.

    PubMed  CAS  Google Scholar 

  • Anderson M. J. (1986) Nerve-induced remodeling of muscle basal lamina during synaptogenesis.J. Cell Biol. 102, 863–877.

    Article  PubMed  CAS  Google Scholar 

  • Anderson M. J. and Cohen M. W. (1977) Nerve-induced and spontaneous redistribution of acetylcholine receptors on cultured muscle cells.J. Physiol. (Lond.) 268, 757–773.

    CAS  Google Scholar 

  • Anderson M. J., Cohen M. W. and Zorychta E. (1977) Effects of innervation on the distribution of acetylcholine receptors on cultured muscle cells.J. Physiol. (Lond.) 268, 731–756.

    CAS  Google Scholar 

  • Anderson M. J., Klier F. G. and Tanguay K. E. (1984) Acetylcholine receptor aggregation parallels the deposition of a basal lamina proteoglycan during development of the neuromuscular junction.J. Cell Biol. 99, 1769–1784.

    Article  PubMed  CAS  Google Scholar 

  • Anderson M.J., Champaneria S., and Swenarchuk L. E. (1991) Synaptic differentiation can be evoked by polymer microbeads that mimic localized pericellular proteolysis by removing proteins from adjacent surfaces.Dev. Biol. 147, 464–479.

    Article  PubMed  CAS  Google Scholar 

  • Anderson M. J., Shi Z. Q., Grawel R. and Zackson S. L. (1995) Erratic deposition of agrin during the formation of Xenopus neuromuscular junctions in culture.Dev. Biol. 170, 1–20.

    Article  PubMed  CAS  Google Scholar 

  • Axelrod D., Ravdin P., Koppel D. E., Schlessinger J., Webb W. W., Elson E. L. and Podleski T. R. (1976) Lateral motion of fluorescently labeled acetylcholine receptors in membranes of developing muscle fibers.Proc. Natl. Acad. Sci. USA 73, 4594–4598.

    Article  PubMed  CAS  Google Scholar 

  • Baker L. P. and Peng H. B. (1993) Tyrosine phosphorylation and acetylcholine receptor cluster formation in cultured Xenopus muscle cells.J. Cell. Biol. 120, 185–195.

    Article  PubMed  CAS  Google Scholar 

  • Baker L. P., Chen Q. and Peng H. B. (1992) Induction of acetylcholine receptor clustering by native polystyrene beads. Implication of an endogenous muscle-derived signalling system.J. Cell Sci. 102, 543–555.

    PubMed  CAS  Google Scholar 

  • Bate M. and Broadie K. (1995) Wiring by fly: The neuromuscular system of the Drosophila embryo.Neuron 15, 513–525.

    Article  PubMed  CAS  Google Scholar 

  • Bennett M. R. and Pettigrew A. G. (1974) The formation of synapses in striated muscle during development.J. Physiol. 241, 515–545.

    PubMed  CAS  Google Scholar 

  • Bigelow J. C., Brown D. C., and Wightman R. M. (1984) γ-aminobutyric acid stimulates the release of endogenous ascorbic acid from rat striatal tissue.J. Neurochem. 42, 412–419.

    Article  PubMed  CAS  Google Scholar 

  • Bixby J. L. (1994) Collagen synthesis inhibition reduces clustering of heparan sulfate proteoglycan and acetylcholine receptors but not agrin or p65, at neuromuscular contacts in vitro.J. Neurobiol. 26, 262–272.

    Article  Google Scholar 

  • Bixby J. L., and Reichardt L. F. (1987) Effects of antibodies to neural cell adhesion molecule (N-CAM) on the differentiation of neuromuscular contacts between ciliary ganglion neurons and myotubesin vitro.Dev. Biol. 119, 363–372.

    Article  PubMed  CAS  Google Scholar 

  • Bloch R. J. and Geiger B. (1980) The localization of acetylcholine receptor clusters in areas of cell-substrate contact in cultures of rat myotubes.Cell 21, 25–35.

    Article  PubMed  CAS  Google Scholar 

  • Bloch R. J. and Morrow J. S. (1989) An unusual betaspectrin associated with clustered acetylcholine receptors.J. Cell Biol. 108, 481–493.

    Article  PubMed  CAS  Google Scholar 

  • Bloch R. J. and Pumplin D. W. (1988) Molecular events in synaptogenesis: nerve-muscle adhesion and postsynaptic differentiation.Am. J. Physiol. 254, C345-C364.

    PubMed  CAS  Google Scholar 

  • Bloch R. J., Resneck W. G., O'Neill A., Strong J. and Pumplin D. W. (1991) Cytoplasmic components of acetylcholine receptor clusters of cultured rat myotubes: the 58-kD protein.J. Cell Biol. 115, 435–446.

    Article  PubMed  CAS  Google Scholar 

  • Bloch R. J., Sealock R., Pumplin D. W., Luther P. W. and Froehner S. C. (1994) Association of acetylcholine receptors with peripheral membrane proteins: evidence from antibody-induced coaggregation.J. Membr. Biol. 138, 13–28.

    PubMed  CAS  Google Scholar 

  • Bowe M. A. and Fallon J. R. (1995) The role of agrin in synapse formation.Annu. Rev. Neurosci. 18, 443–462.

    Article  PubMed  CAS  Google Scholar 

  • Bowe M. A., Deyst K. A., Leszyk J. D., and Fallon J. R. (1994) Identification and purification of an agrin receptor from Torpedo postsynaptic membranes: a heteromeric complex related to the dystroglycans.Neuron. 12, 1173–1180.

    Article  PubMed  CAS  Google Scholar 

  • Bowen D. C., Sugiyama J., Ferns M. and Hall Z. (1996) Neural agrin activates a high-affinity receptor in C2 muscle cells that is unresponsive to muscle agrin.J. Neurosci. 16, 3791–3797.

    PubMed  CAS  Google Scholar 

  • Bozyczko E., Decker C., Muschler J. and Horwitz A. F. (1989) Integrin in developing and adult skeletal muscle.Exp. Cell Res. 183, 72–91.

    Article  PubMed  CAS  Google Scholar 

  • Brenner H. R., Herczeg R. A. and Slater C. R. (1992) Synapse-specific expression of acetylcholine receptor genes and their products at original synaptic sites in the absence of innervation.Development 116, 41–53.

    PubMed  CAS  Google Scholar 

  • Burden S. J., Sargent P. B. and McMahan U. J. (1979) Acetylcholine receptors in regenerating muscle accumulate at original synaptic sites in the absence of the nerve.J. Cell Biol. 82, 412–425.

    Article  PubMed  CAS  Google Scholar 

  • Burg M. A., Halfter W. and Cole G. J. (1995) Analysis of proteoglycan expression in developing chicken brain: characterization of a heparan sulfate proteoglycan that interacts with the neural cell adhesion molecule.J. Neurosci. Res. 41, 49–64.

    Article  PubMed  CAS  Google Scholar 

  • Burns J. J., Rivers J. M., and Machlin L. J. (eds.) (1987)Third Conference on Vitamin C. The New York Academy of Sciences, New York.

    Google Scholar 

  • Burry R. W., (1980) Formation of apparent presynaptic elements in response to poly-basic compounds.Brain Res. 184, 85–98.

    Article  PubMed  CAS  Google Scholar 

  • Campagna J. A., Ruegg M. A. and Bixby J. L. (1995) Agrin is a differentiation-inducing “stop signal” for motorneurons in vitro.Neuron 15, 1365–1374.

    Article  PubMed  CAS  Google Scholar 

  • Campanelli J. T., Hoch W., Rupp F., Kreiner T. and Scheller R. H. (1991) Agrin mediates cell contact-induced acetylcholine receptor clustering.Cell 67, 909–916.

    Article  PubMed  CAS  Google Scholar 

  • Campanelli J. T., Roberds S. L., Campbell K. P. and Scheller R. H. (1994) A role for dystrophin-associated glycoproteins and utrophin in agrin-induced AChR clustering.Cell 77, 663–674.

    Article  PubMed  CAS  Google Scholar 

  • Champaneria S., Swenarchuk L. E. and Anderson M. J. (1992) Increases in pericellular proteolysis at developing neuromuscular junctions in culture.Dev. Biol. 149, 261–277.

    Article  PubMed  CAS  Google Scholar 

  • Chiu A. Y. and Sanes J. R. (1984) Development of basal lamina in synaptic and extrasynaptic portions of embryonic rat muscle.Dev. Biol. 103, 456–467.

    Article  PubMed  CAS  Google Scholar 

  • Chow I. (1990) Cell-cell interaction during synaptogenesis.J. Physiol. (Paris)84, 121–127.

    CAS  Google Scholar 

  • Chow I. and Poo M. M. (1985) Release of acetylcholine from embryonic neurons upon contact with muscle cell.J. Neurosci. 5, 1076–1082.

    PubMed  CAS  Google Scholar 

  • Christian C. N., Daniels M. P., Sugiyama H., Vogel Z., Jacques L. and Nelson P. G. (1978) A factor from neurons increases the number of acetylcholine receptor aggregates on cultured muscle cells.Proc. Natl. Acad. Sci. USA 75, 4011–4015.

    Article  PubMed  CAS  Google Scholar 

  • Cohen M. W., Rodriguez-Marin E. and Wilson E. M. (1987) Distribution of synaptic specializations along isolated motor units formed in Xenopus nerve-muscle cultures.J. Neurosci. 7, 2849–2861.

    PubMed  CAS  Google Scholar 

  • Cohen M. W., Jones O. T., and Angelides K. J. (1991) Distribution of Ca2+ channels on frog motor nerve terminals revealed by fluorescent omegaconotoxin.J. Neurosci. 11, 1032–1039.

    PubMed  CAS  Google Scholar 

  • Cohen M. W. and Godfrey F. W. (1992) Early appearance of and neuronal contribution to agrin-like molecules at embryonic frog nervemuscle synapses formed in culture.J. Neurosci. 12, 2982–2992.

    PubMed  CAS  Google Scholar 

  • Cohen M. W., Moody-Corbett F. and Godfrey E. W. (1995a) Former neuritic pathways containing endogenous neural agrin have high synaptogenic activity.Dev. Biol. 167, 458–468.

    Article  PubMed  CAS  Google Scholar 

  • Cohen M. W., Jacobson C., Godfrey E. W., Campbell K. P. and Carbonetto S. (1995b) Distribution of alpha-dystroglycan during embryonic nervemuscle synaptogenesis.J. Cell Biol. 129, 1093–1101.

    Article  PubMed  CAS  Google Scholar 

  • Connold A. L., Evers J. V. and Vrbova G. (1986) Effect of calcium and protease inhibitors on synapse elimination during postnatal development in the rat soleus muscle.Dev. Brain Res. 28, 99–107.

    Article  CAS  Google Scholar 

  • Corfas G., Falls D. L. and Fischbach G. D. (1993) ARIA, a protein that stimulates acetylcholine receptor synthesis, also induces tyrosine phosphorylation of a 185-kDa muscle transmembrane protein.Proc. Natl. Acad. Sci. USA 90, 1624–1628.

    Article  PubMed  CAS  Google Scholar 

  • Covault J. and Sanes J. R. (1985) Neural cell adhesion molecule (N-CAM) accumulates in denervated and paralyzed skeletal muscles.Proc. Natl. Acad. Sci. USA 82, 4544–4548.

    Article  PubMed  CAS  Google Scholar 

  • Covault J. and Sanes J. R. (1986) Distribution of N-CAM in synaptic and extrasynaptic portions of developing and adult skeletal muscle.J. Cell Biol. 102, 716–730.

    Article  PubMed  CAS  Google Scholar 

  • Daggett D. F., Cohen M. W., Stone D., Nikolics K., Rauvala H. and Peng H. B. (1996) The role of agrin-growth factor interaction in ACh receptor clustering.Mol. Cell. Neurosci. 8, 272–285.

    Article  PubMed  CAS  Google Scholar 

  • Dai Z. and Peng H. B. (1993) Elevation in presynaptic Ca2+ level accompanying initial nervemuscle contact in tissue culture.Neuron 10, 827–837.

    Article  PubMed  CAS  Google Scholar 

  • Dai Z. and Peng H. B. (1995) Presynaptic differentiation induced in cultured neurons by local application of basic fibroblast growth factor.J. Neurosci. 15, 5466–5475.

    PubMed  CAS  Google Scholar 

  • Dai Z. and Peng H. B. (1996) Dynamics of synaptic vesicles in cultured spinal cord neurons in relationship to synaptogenesis.Mol. Cell. Neurosci. 7, 443–452.

    Article  PubMed  CAS  Google Scholar 

  • Dai Z., Scotland P. B., Froehner S. C. and Peng H. B. (1996) Association of phosphotyrosine with rapsyn expression in Xenopus embryonic cells.Neuro Report. 7, 657–661.

    CAS  Google Scholar 

  • Dan Y. and Poo M. M. (1994) Retrograde interactions during formation and elimination of neuromuscular synapses.Curr. Opin. Neurobiol. 4, 95–100.

    Article  PubMed  CAS  Google Scholar 

  • Daniels M. P., Krikorian J. G., Ling A. and Olek A. J. (1987) Neural factor-induced formation of acetylcholine receptor aggregates on myotubes: An in vitro model for development of the postsynaptic cell surface complex, in:Model Systems of Development and Aging of the Nervous System (Vernadakis A., Privat A., Lauder J. M., Timiras P. S., and Giacobini E., eds.), Martinus Nijhoff, Boston, p. 335.

    Google Scholar 

  • Daniels M. P., Krikorian J. G., Olek A. J. and Bloch R. J. (1990) Association of cytoskeletal proteins with newly formed acetylcholine receptor aggregates induced by embryonic brain extract.Exp. Cell Res. 186, 99–108.

    Article  PubMed  CAS  Google Scholar 

  • DeChiara T. M., Bowen D. C., Valenzuela D. M., Simmons M. V., Poueymirou W. T., Thomas S., Kinetz E., Compton D. L., Rojas E., Park J. S., Smith C., DiStefano P. S., Glass D. J., Burden S. J. and Yancopoulos G. D. (1996) The receptor tyrosine kinase MuSK is required for neuromuscular junction formation in vivo.Cell 85, 501–512.

    Article  PubMed  CAS  Google Scholar 

  • Dennis M. J., Ziskind-Conhaim L., and Harris A. J. (1981) Development of neuromuscular junctions in rat embryos.Dev. Biol. 81, 266–279.

    Article  PubMed  CAS  Google Scholar 

  • Denzer A. J., Gesemann M., Schumacher B., and Ruegg M. A. (1995) An amino-terminal extension is required for the secretion of chick agrin and its binding to extracellular matrix.J. Cell Biol. 131, 1547–1560.

    Article  PubMed  CAS  Google Scholar 

  • Dubinsky J. M., Loftus D. J., Fischbach G. D., and Elson E. L. (1989) Formation of acetylcholine receptor clusters in chick myotubes: migration or new insertion?J. Cell Biol. 109, 1733–1743.

    Article  PubMed  CAS  Google Scholar 

  • Dutton E. K., Uhm C. S., Samuelsson S. J., Schaffner A. E., Fitzgerald S. C. and Daniels M. P. (1995) Acetylcholine receptor aggregation at nervemuscle contacts in mammalian cultures: induction by ventral spinal cord neurons is specific to axons.J. Neurosci. 15, 7401–7416.

    PubMed  CAS  Google Scholar 

  • Ehlers M. D., Mammen A. L., Lau L. F. and Huganir R. L. (1996) Synaptic targeting of glutamate receptors.Curr. Opinion Cell Biol. 8, 484–489.

    Article  PubMed  CAS  Google Scholar 

  • Ervasti J. M. and Campbell K. P. (1991) Membrane orgnization of the dystrophin-glycoprotein complex.Cell 68, 1121–1131.

    Article  Google Scholar 

  • Fallon J. R., Nitkin R. M., Reist N. E., Wallace B. G. and McMahan U. J. (1985) Acetylcholine receptor-aggregating factor is similar to molecules concentrated at neuromuscular junctions.Nature 315, 571–574.

    Article  PubMed  CAS  Google Scholar 

  • Falls D. L., Rosen K. M., Corfas G., Lane W. S. and Fischbach G. D. (1993) ARIA, a protein that stimulates acetylcholine receptor synthesis, is a member of the neu ligand family.Cell 72, 801–815.

    Article  PubMed  CAS  Google Scholar 

  • Ferns M., Hoch W., Campanelli J. T., Rupp F., Hall Z. W. and Scheller R. H. (1992) RNA splicing regulates agrin-mediated acetylcholine receptor clustering activity on cultured myotubes.Neuron 8, 1079–1086.

    Article  PubMed  CAS  Google Scholar 

  • Ferns M., Deiner M. and Hall Z. (1996) Agrin-induced acetylcholine receptor clustering in mammalian muscle requires tyrosine phosphorylation.J. Cell Biol. 143, 937–944.

    Article  Google Scholar 

  • Ferns M. J., Campanelli J. T., Hoch W., Scheller R. H., and Hall Z. (1993) The ability of agrin to cluster AChRs depends on alternative splicing and on cell surface proteoglycans.Neuron 11, 491–502.

    Article  PubMed  CAS  Google Scholar 

  • Festoff B. W., Rao J. S., Reddy B. R. and Hantai D. (1990) A cascade approach to synapse formation based on thrombogenic and fibrinolytic models, inNATO Advanced Research Workshop on Regulation of Extravascular Fibrinolysis in Nervous System Development and Disease (1989: Maratea, Italy) (Festoff B. W.). Plenum, New York, p. 245.

    Google Scholar 

  • Fischbach G. D. (1972) Synapse formation between dissociated nerve and muscle cells in low density cell cultures.Dev. Biol. 28, 407–429.

    Article  PubMed  CAS  Google Scholar 

  • Fischbach G. D., Aratake H., Corfas G., Falls D. L., Goodearl A. and Rosen K. M. (1994) Trophic interactions at developing synapses.Prog. Clin. Biol. Res. 390, 173–190.

    PubMed  CAS  Google Scholar 

  • Fontaine B., Klarsfeld A., Hokfelt T. and Changeux J. P. (1986) Calcitonin gene-related peptide, a peptide present in spinal cord motoneurons, increases the number of acetylcholine receptors in primary cultures of chick embryo myotubes.Neurosci. Lett. 71, 59–65.

    Article  PubMed  CAS  Google Scholar 

  • Fontaine B., Klarsfeld A. and Changeux J. P. (1987) Calcitonin gene-related peptide and muscle activity regulate acetylcholine receptor alpha-subunit mRNA levels by distinct intracellular pathways.J. Cell Biol. 105, 1337–1342.

    Article  PubMed  CAS  Google Scholar 

  • Frank E. and Fischbach G. D. (1979) Early events in neuromuscular junction formation in vitro: induction of acetylcholine receptor clusters in the postsynaptic membrane and morphology of newly formed synapses.J. Cell Biol. 83, 143–158.

    Article  PubMed  CAS  Google Scholar 

  • Froehner S. C. (1991) The submembrane machinery for nicotinic acetylcholine receptor clustering.J. Cell Biol. 114, 1–7.

    Article  PubMed  CAS  Google Scholar 

  • Funte L. R. and Haydon P. G. (1993) Synaptic target contact enhances presynaptic calcium influx by activating cAMP-dependent protein kinase during synaptogenesis.Neuron,10, 1069–1078.

    Article  PubMed  CAS  Google Scholar 

  • Ganju P., Walls E., Brennan J. and Reith A. D. (1995) Cloning and developmental expression of Nsk2, a novel receptor tyrosine kinase implicated in skeletal myogenesis.Oncogene 11, 281–290.

    PubMed  CAS  Google Scholar 

  • Gautam M., Noakes P. G., Mudd J., Nichol M., Chu G. C., Sanes J. R., and Merlie J. P. (1995) Failure of postsynaptic specialization to develop at neuromuscular junctions of rapsyn-deficient mice.Nature 377, 232–236.

    Article  PubMed  CAS  Google Scholar 

  • Gautam M., Noakes P. G., Moscoso L., Rupp F., Scheller R. H., Merlie J. P. and Sanes J. R. (1996) Defective neuromuscular synaptogenesis in agrin-deficient mutant mice.Cell 85, 525–535.

    Article  PubMed  CAS  Google Scholar 

  • Gee S. H., Montanaro F., Lindenbaum M. H. and Carbonetto S. (1994) Dystroglycan-α, a dystrophin-associated glycoprotein, is a functional agrin receptor.Cell 77, 675–686.

    Article  PubMed  CAS  Google Scholar 

  • Gesemann M., Denzer A. J. and Ruegg M. A. (1995) Acetylcholine receptor-aggregating activity of agrin isoforms and mapping of the active site.J. Cell Biol. 128, 625–636.

    Article  PubMed  CAS  Google Scholar 

  • Gesemann M., Cavalli V., Denzer A. J., Brancaccio A., Schumacher B. and Ruegg M. A. (1996) Alternative splicing of agrin alters its binding to heparin, dystroglycan, and he putative agrin receptor.Neuron 16, 1–20.

    Article  Google Scholar 

  • Gillespie S. K. H., Balasubramanian S., Fung E. T. and Huganir R. L. (1996). Rapsyn clusters and activates the synapse-specific receptor tyrosine kinase MuSK.Neuron 16, 953–962.

    Article  PubMed  CAS  Google Scholar 

  • Glass D. J., Bowen D. C., Stitt T. N., Radziejewski C., Bruno J., Ryan T. E., Gies D. R., Shah S., Mattsson L., Burden S. J., DiStefano P. S., Valenzuela D. M., DeChiara T. M., and Yancopoulos G. D. (1996) Agrin acts via a MuSK receptor complex.Cell 85, 513–523.

    Article  PubMed  CAS  Google Scholar 

  • Glicksman M. A. and Sanes J. R. (1983) Differentiation of motor nerve terminals formed in the absence of muscle fibres.J. Neurocytol. 12, 661–671.

    Article  PubMed  CAS  Google Scholar 

  • Godfrey E. W., Nitkin R. M., Wallace B. G., Rubin L. L. and McMahan U. J. (1984) Components of Torpedo electric organ and muscle that cause aggregation of acetylcholine receptors on cultured muscle cells.J. Cell Biol. 99, 615–627.

    Article  PubMed  CAS  Google Scholar 

  • Godfrey E. W., Siebenlist R. E., Wallskog P. A., Walters L. M., Bolender D. L. and Yorde D. E. (1988) Basal lamina components are concentrated in premuscle masses and at early acetylcholine receptor clusters in chick embryo hindlimb muscles.Dev. Biol. 130, 471–486.

    Article  PubMed  CAS  Google Scholar 

  • Goldman D. B., Carlson M. and Staple J. (1991) Induction of adult-type nicotinic acetylchooline receptor gene expression in noninervated regenerating muscle.Neuron 7, 649–658.

    Article  PubMed  CAS  Google Scholar 

  • Gonzales A-M., Buscaglia M., Ong M., and Baird A. (1990) Distribution of basic fibroblast growth factor in the 18-day rat fetus: localization in the basement membranes of diverse tissues.J. Cell Biol. 110, 753–765.

    Article  Google Scholar 

  • Goodearl A. D. J., Yee A. G., Sandrock A. W., Jr., Corfas G. and Fischbach G. D. (1995). ARIA is concentrated in the synaptic basal lamina of the developing chick neuromuscular junction.J. Cell Biol. 130, 1423–1434.

    Article  PubMed  CAS  Google Scholar 

  • Gordon H., Lupa M., Bowen D. and Hall Z. (1993) A muscle cell variant defective in glycosaminoglycan biosynthesis forms nerve-induced but not spontaneous clusters of the acetylcholine receptor and the 43 kDa protein.J. Neurosci. 13, 586–595.

    PubMed  CAS  Google Scholar 

  • Grinnell A. D. (1995) Dynamics of nerve-muscle interaction in developing and mature neuromuscular junctions.Physiol. Rev. 75, 789–824.

    PubMed  CAS  Google Scholar 

  • Grumet M., Rutishauser U. and Edelman G. M. (1982) Neural cell adhesion molecule is on embryonic muscle cells and mediates adhesion to nerve cells in vitro.Nature 295, 693–695.

    Article  PubMed  CAS  Google Scholar 

  • Hall Z. W. and Sanes J. R. (1993) Synaptic structure and development: the neuromuscular junction.Cell 72 (Suppl.), 99–121.

    Article  PubMed  Google Scholar 

  • Hatta K., Takagi S., Fujisawa H. and Takeichi M. (1987) Spatial and temporal expression pattern of N-cadherin cell adhesion molecules correlated with morphogenetic processes of chicken embryos.Dev. Biol. 120, 215–227.

    Article  PubMed  CAS  Google Scholar 

  • Haydon P. G. and Zoran M. J. (1994) Retrograde regulation of presynaptic development during synaptogenesis.J. Neurobiol. 25, 694–706.

    Article  PubMed  CAS  Google Scholar 

  • Henderson C. E., Camu W., Mettling C., Gouin A., Poulsen K., Karihaloo M., Rullamas J., Evens T., MacMahon S. B., Armanini M. P., Berkemeir L., Phillips H. S. and Rosenthal A. (1993) Neurotrophins promote motor neuron survival and are present in embryonic limb bud.Nature 363, 268–270.

    Article  Google Scholar 

  • Heuser J. E., Reese T. S., Dennis M. J., Jan Y., Jan L., and Evans L. (1979) Synaptic vesicle exocytosis captured by quick freezing and correlated with quantal transmitter release.J. Cell Biol. 81, 275–300.

    Article  PubMed  CAS  Google Scholar 

  • Hirano H. (1967) Ultrastructural study on the morphogenesis of the neuromuscular junction in the skeletal muscle of the chick.Z. Zellforsch. Mikrosk. Anat. 79, 198–208.

    Article  PubMed  CAS  Google Scholar 

  • Holmes W. E., Sliwkowski M. X., Akita R. W., Henzel W. J., Lee J., Park J. W., Yansura D., Abadi N. T., Raab H., Lewis G. D., Shepard H. M., Kuang W.-J., Wood W. J., Goeddel D. V. and Vandlen R. L. (1992) Identification of heregulin, a specific activator of p185erB2.Science 256, 1205–1210.

    Article  PubMed  CAS  Google Scholar 

  • Hornig D. (1975) Distribution of ascorbic acid, metabolites, and analogues in man and animals.Ann. NY Acad. Sci. 258, 103–118.

    Article  PubMed  CAS  Google Scholar 

  • Horovitz O., Spitsberg V. and Salpeter M. M. (1989a) Regulation of acetylcholine receptor synthesis at the level of translation in rat primary muscle cells.J. Cell Biol. 108, 1817–1822.

    Article  PubMed  CAS  Google Scholar 

  • Horovitz O., Knaack D., Podleski T. R. and Salpeter M. M. (1989b) Acetylcholine receptor alpha-subunit mRNA is increased by ascorbic acid in cloned L5 muscle cells: Northern blot analysis and in situ hybridization.J. Cell Biol. 108, 1823–1832.

    Article  PubMed  CAS  Google Scholar 

  • Hume R. I., Role L. W. and Fischbach G. D. (1983) Acetylcholine release from growth cones detected with patches of acetylcholine receptor-rich membranes.Nature 305, 632–634.

    Article  PubMed  CAS  Google Scholar 

  • Hunter D. D., Shah V., Merlie J. P. and Sanes J. R. (1989a) A laminin-like adhesive protein concentrated in the synaptic cleft of the neuromuscular junction.Nature 338, 229–234.

    Article  PubMed  CAS  Google Scholar 

  • Hunter D. D., Porter B. E., Bulock J. W., Adams S. P., Merlie J. P. and Sanes J. R. (1989b) Primary sequence of a motor neuron-selective adhesive site in the synaptic basal lamina protein S-laminin.Cell 59, 905–913.

    Article  PubMed  CAS  Google Scholar 

  • Hunter D. D., Cashman N., Morris-Valero R., Bulock J. W., Adams S. P. and Sanes J. R. (1991) An LRE (leucine-arginine-glutamate)-dependent mechanism for adhesion of neurons to S-laminin.J. Neurosci. 11, 3960–3971.

    PubMed  CAS  Google Scholar 

  • Ishikawa Y. and Shimada Y. (1982) Acetylcholine receptors and cholinesterase in developing chick skeletal muscle fibers.Brain Res. 281, 187–197.

    PubMed  CAS  Google Scholar 

  • James D. W. and Tresman R. L. (1969) An electron-microscopic study of the de novo formation of neuromuscular junctions in tissue culture.Z. Zellforsch. Mikrosk. Anat. 100, 126–140.

    Article  PubMed  CAS  Google Scholar 

  • Jannings C. G., Dyer S. M. and Burden S. J. (1993) Muscle-specific trk-related receptor with a kringle domain defines a distinct class of receptor tyrosine kinases.Proc. Natl. Acad. Sci. USA 90, 2895–2899.

    Article  Google Scholar 

  • Jessell T. M., Siegel R. E., and Fischbach G. D. (1979) Induction of acetylcholine receptors on cultuted skeletal muscle by a factor extracted from brain and spinal cord.Proc. Natl. Acad. Sci. USA 76, 5397–5401.

    Article  PubMed  CAS  Google Scholar 

  • Jo S. A. and Burden S. J. (1992) Synaptic basal lamina contains a signal for synapse-specific transcription.Development 115, 673–680.

    PubMed  CAS  Google Scholar 

  • Jo S. A., Zhu X., Marchionni M. A. and Burden S. J. (1995) Neuregulins are concentrated at nervemuscle synapses and activate ACh-receptor gene expression.Nature 373, 158–161.

    Article  PubMed  CAS  Google Scholar 

  • Jones G., Herczeg A., Ruegg M. A., Lichtsteiner M., Kröger S. and Brenner H. R. (1996) Substrate-bound agrin induces expression of acetylcholine receptor e-subunit gene in cultured mammalian muscle cells.Proc. Natl. Acad. Sci. USA 93, 5985–5990.

    Article  PubMed  CAS  Google Scholar 

  • Kalcheim C., Vogel Z. and Duksin D. (1982a) Embryonic brain extract induces collagen biosynthesis in cultured muscle cells: involvement in acetylcholine receptor aggregation.Proc. Natl. Acad. Sci. USA 79, 3077–3081.

    Article  PubMed  CAS  Google Scholar 

  • Kalcheim C., Duksin D. and Vogel Z. (1982b) Aggregation of acetylcholine receptors in nervemuscle cocultures is decreased by inhibitors of collagen production.Neurosci. Lett. 31, 265–270.

    Article  PubMed  CAS  Google Scholar 

  • Kalcheim C., Duksin D. and Vogel Z. (1982c) Involvement of collagen in the aggregation of acetylcholine receptors on cultured muscle cells.J. Biol. Chem. 257, 12,722–12,727.

    CAS  Google Scholar 

  • Kalcheim C., Bachar E., Duksin D. and Vogel Z. (1985) Ciliary ganglia and spinal cord explants release an ascorbate-like compound which stimulates proline hydroxylation and collagen formation in muscle cultures.Neurosci. Lett. 58, 219–224.

    Article  PubMed  CAS  Google Scholar 

  • Kelly A. M. and Zacks S. I. (1969) The fine structure of motor endplate morphogenesis.J. Cell Biol. 42, 154–169.

    Article  PubMed  CAS  Google Scholar 

  • Kelly R. B. (1993) Storage and release of neurotrans-mitters.Cell 72, 43–53.

    Article  PubMed  Google Scholar 

  • Kidokoro Y. and Yeh E. (1982) Initial synaptic transmission at the growth cone in Xenopus nervemuscle cultures.Proc. Natl. Acad. Sci. USA 79, 6727–6731.

    Article  PubMed  CAS  Google Scholar 

  • Kleiman R. J. and Reichardt L. F. (1996) Testing the agrin hypothesis.Cell 85, 461–464.

    Article  PubMed  CAS  Google Scholar 

  • Knaack D. and Podleski T. R. (1985) Ascorbic acid mediates acetylcholine receptor increase induced by brain extract in L5 myogenic cells.Proc. Natl. Acad. Sci. USA 82, 575–579.

    Article  PubMed  CAS  Google Scholar 

  • Knaack D., Shen I., Salpeter M. M. and Podleski T. R. (1986) Selective effects of ascorbic acid on acetylcholine receptor number and distribution.J. Cell Biol. 102, 795–802.

    Article  PubMed  CAS  Google Scholar 

  • Koliatsos V. E., Clatterbuck R. E., Windslow J. W., Cayouette M. H. and Price D. L. (1993) Evidence that brain-derived neurotrophic factor is a trophic factor for motor neuronsin vivo.Neuron 10, 359–367.

    Article  PubMed  CAS  Google Scholar 

  • Kopczynski C. C., Davis G. H. and Goodman C. S. (1996) A neural tetraspanin, encoded by late bloomer, that facilitates synapse formation.Science 271, 1867–1870.

    Article  PubMed  CAS  Google Scholar 

  • Krystosek A. and Seeds N. W. (1984) Peripheral neurons and Schwann cells secrete plasminogen activator.J. Cell Biol. 98, 773–776.

    Article  PubMed  CAS  Google Scholar 

  • Kuffler D. P. (1986) Accurate reinnervation of motor endplates after disruption of sheath cells and muscle fibers.J. Comp. Neurol. 250, 228–235.

    Article  PubMed  CAS  Google Scholar 

  • Kuhse J., Betz H. and Kirsch J. (1995) The inhibitory glycine receptor: architecture, synaptic localization and molecular pathology of a postsynaptic ion-channel complex.Curr. Opinion Neurobiol. 5, 318–323.

    Article  CAS  Google Scholar 

  • Kullberg R. W., Lentz T. L., and Cohen M. W. (1977) Development of the myotomal neuromuscular junction in Xenopus laevis: an electrophysiological and fine-structural study.Dev. Biol. 60, 101–129.

    Article  PubMed  CAS  Google Scholar 

  • Landmesser L., Dahm L., Schultz K. and Rutishauser U. (1988) Distinct roles for adhesion molecules during innervation of embryonic chick muscle.Dev. Biol. 130, 645–670.

    Article  PubMed  CAS  Google Scholar 

  • Laufer R. and Changeux J. P. (1987) Calcitonin generelated peptide elevates cyclic AMP levels in chick skeletal muscle: possible neurotrophic role for a coexisting neuronal messenger.EMBO J. 6, 901–906.

    PubMed  CAS  Google Scholar 

  • Liu Y., Fields R. D., Festoff B. W. and Nelson P. G. (1994a) Proteolytic action of thrombin is required for electrical activity-dependent synapse reduction.Proc. Natl. Acad. Sci. USA 91, 10,300–10,304.

    CAS  Google Scholar 

  • Liu Y., Fields R. D., Fitzgerald S., Festoff B. W. and Nelson P. G. (1994b) Proteolytic activity, synapse elimination, and the Hebb synapse.J. Neurobiol. 25, 325–335.

    Article  PubMed  CAS  Google Scholar 

  • Loeb J. A. and Fischbach G. D. (1995) ARIA can be released from extracellular matrix through cleavage of a heparin-binding domain.J. Cell Biol. 130, 127–135.

    Article  PubMed  CAS  Google Scholar 

  • Ma E., Morgan R. and Godfrey E. W. (1995) Agrin mRNA variants are differentially regulated in developing chick embryo spinal cord and sensory ganglia.J. Neurobiol. 26, 585–597.

    Article  PubMed  CAS  Google Scholar 

  • Magill-Solc C. and McMahan U. J. (1988) Motor neurons contain agrin-like molecules.J. Cell Biol. 107, 1825–1833.

    Article  PubMed  CAS  Google Scholar 

  • Magill-Solc C. and McMahan U. J. (1990) Synthesis and transport of agrin-like molecules in motor neurons.J. Exp. Biol. 153, 1–10.

    PubMed  CAS  Google Scholar 

  • Marchionni M. A., Goodearl A. D., Chen M. S., Bermingham-McDonough O., Kirk C., Hendricks M., Danehy F., Misumi D., Sudhalter J., Kobayashi K., Wroblewski D., Lynch C., Baldasare M., Hiles I., Davis J. B., Hsuan J. J., Totty N. F., Otsu M., McBurney R. N., Waterfield M. D., Stroobant P., and Gwynne D. (1993) Ghal growth factors are alternatively spliced erB2 ligands expressed in the nervous system.Nature 362, 312–318.

    Article  PubMed  CAS  Google Scholar 

  • Martin P. T., Ettinger A. J. and Sanes J. R. (1995) A synaptic localization domain in the synaptic cleft protein laminin beta 2 (s-laminin).Science 269, 413–416.

    Article  PubMed  CAS  Google Scholar 

  • Martin P. T., Kaufman S. J., Kramer R. H. and Sanes J. R. (1996) Synaptic integrins in developing, adult, and mutant muscle: selective association of α1, α7A, and α7B integrins with the neuromuscular junction.Dev. Biol. 174, 125–139.

    Article  PubMed  CAS  Google Scholar 

  • Martinou J. C., Falls D. L., Fischbach G. D. and Merlie J. P. (1991) Acetylcholine receptor-inducing activity stimulates expression of the epsilon-subunit gene of the muscle acetylcholine receptor.Proc. Natl. Acad. Sci. USA 88, 7669–7673.

    Article  PubMed  CAS  Google Scholar 

  • Mason R. T., Peterfreund R. A., Sawchenko P. E., Corrigan A. Z., Rivier J. E. and Vale W. W. (1984) Release of the predicted calcitonin gene-related peptide from cultured rat trigeminal ganglion cells.Nature 308, 653–655.

    Article  PubMed  CAS  Google Scholar 

  • McMahan U. J. (1990) The agrin hypothesis.Cold Spring. Harb. Symp. Quant. Biol. 55, 407–418.

    PubMed  CAS  Google Scholar 

  • McMahan U. J., Horton S. E., Werle M. J., Honig L. S., Kroger S., Ruegg M. A. and Escher G. (1992) Agrin isoforms and their role in synaptogenesis.Curr. Opinion Cell Biol. 4, 869–874.

    Article  PubMed  CAS  Google Scholar 

  • Meier T., Perez G. M. and Wallace B. G. (1995) Immobilization of nicotinic acetylcholine receptors in mouse C2 myotubes by agrin-induced protein tyrosine phosphorylation.J. Cell Biol. 131, 441–451.

    Article  PubMed  CAS  Google Scholar 

  • Meier T., Gesemann M., Cavalli V., Ruegg M. A. and Wallace B. G. (1996) AChR phosphorylation and aggregation induced by an agrin fragment that lacks the binding domain for α-dystroglycan.EMBO J.,15, 2625–2631.

    PubMed  CAS  Google Scholar 

  • Milby K. H., Mefford I. N., Chey W. and Adams R. N. (1981)In vitro andin vivo depolarization coupled efflux of ascorbic acid in rat brain preparations.Brain Res. Bull. 7, 237–242.

    Article  PubMed  CAS  Google Scholar 

  • Moscoso L. M., Chu G. C., Gautam M., Noakes P. G., Merlie J. P. and Sanes J. R. (1995) Synapse-associated expression of an acetylcholine receptor-inducing protein, ARIA/heregulin, and its putative receptors, ErbB2 and ErbB3, in developing mammalian muscle.Dev. Biol. 172, 158–169.

    Article  PubMed  CAS  Google Scholar 

  • Nakajima Y., Kidokoro Y. and Klier F. G. (1980) The development of functional neuromuscular junctions in vitro: an ultrastructural and physiological study.Dev. Biol. 77, 52–72.

    Article  PubMed  CAS  Google Scholar 

  • New H. V. and Mudge A. W. (1986) Calcitonin gene-related peptide regulates muscle acetylcholine receptor synthesis.Nature 323, 809–811.

    Article  PubMed  CAS  Google Scholar 

  • Nitkin R. M. and Rothschild T. C. (1990) Agrin-induced reorganization of extracellular matrix components on cultured myotubes: relationship to AChR aggregation.J. Cell Biol. 111, 1161–1170.

    Article  PubMed  CAS  Google Scholar 

  • Nitkin R. M., Smith M. A., Magill C., Fallon J. R., Yao Y. M., Wallace B. G. and McMahan U. J. (1987) Identification of agrin, a synaptic organizing protein from Torpedo electric organ.J. Cell Biol. 105, 2471–2478.

    Article  PubMed  CAS  Google Scholar 

  • Noakes P. G., Gautam M., Mudd J., Sanes J. R., and Merlie J. P. (1995) Aberrant differentiation of neuromuscular junctions in mice lacking s-laminin/laminin beta 2.Nature 374, 258–262.

    Article  PubMed  CAS  Google Scholar 

  • O'Brien R. A. D., Ostberg A. J. C. and Vrbova G. (1984) Protease inhibitors reduce the loss of nerve terminals induced by activity and calcium in developing rat soleus muscles in vitro.Neuroscience 12, 637–646.

    Article  PubMed  Google Scholar 

  • Parsons J. T., Schaller M. D., Hildebrand J., Leu T.-H., Richardson A. and Otey C. (1994) Focal adhesion kinase: structure and signalling.J. Cell Sci. Suppl. 18, 109–113.

    PubMed  CAS  Google Scholar 

  • Peng H. B. (1986) Elimination of preexistent acetylcholine receptor clusters induced by the formation of new clusters in the absence of nerve.J. Neurosci. 6, 581–589.

    PubMed  CAS  Google Scholar 

  • Peng H. B., Nakajima Y. and Bridgman P. C. (1980) Development of the postsynaptic membrane in Xenopus neuromuscular cultures observed by freeze-fracture and thin-section electron microscopy.Brain Res. 196, 11–31.

    Article  PubMed  CAS  Google Scholar 

  • Peng H. B., Cheng P. C. and Luther P. W. (1981) Formation of ACh receptor clusters induced by positively charged latex beads.Nature 292, 831–834.

    Article  PubMed  CAS  Google Scholar 

  • Peng H. B., Markey D. R., Muhlach W. L., and Pollack E. D. (1987) Development of presynaptic specializations induced by basic polypeptidecoated latex beads in spinal cord cultures.Synapse. 1, 10–19.

    Article  PubMed  CAS  Google Scholar 

  • Peng H. B., Chen Q. M., de Biasi S. and Zhu D. L. (1989) Development of calcitonin gene-related peptide (CGRP) immunoreactivity in relationship to the formation of neuromuscular junctions in Xenopus myotomal muscle.J. Comp. Neurol. 290, 533–543.

    Article  PubMed  CAS  Google Scholar 

  • Peng H. B., Baker L. P. and Chen Q. (1991) Induction of synaptic development in cultured muscle cells by basic fibroblast growth factor.Neuron 6, 237–246.

    Article  PubMed  CAS  Google Scholar 

  • Peng H. B., Baker L. P. and Dai Z. (1993) A role of tyrosine phosphorylation in the formation of acetylcholine receptor clusters induced by electric fields in cultured Xenopus muscle cells.J. Cell Biol. 120, 197–204.

    Article  PubMed  CAS  Google Scholar 

  • Peng H. B., Ali A. A., Dai Z., Daggett D. F., Raulo E., and Rauvala H. (1995) The role of heparin-binding growth-associated molecule (HB-GAM) in the postsynaptic induction in cultured muscle cells.J. Neurosci. 15, 3027–3038.

    PubMed  CAS  Google Scholar 

  • Pittmann R. N. (1985) Release of plasminogen activator and a calcium-dependent metalloprotease from cultured sympathetic and sensory neurons.Dev. Biol. 110, 91–101.

    Article  Google Scholar 

  • Podleski T. R., Axelrod D., Ravdin P., Greenberg I., Johnson M. M. and Salpeter M. M., (1978) Nerve extract induces increase and redistribution of acetylcholine receptors on cloned muscle cells.Proc. Natl. Acad. Sci. USA 75, 2035–2039.

    Article  PubMed  CAS  Google Scholar 

  • Porter B. E., Weis J. and Sanes J. R. (1995) A motoneuron-selective stop signal in the synaptic protein S-laminin.Neuron 14, 549–559.

    Article  PubMed  CAS  Google Scholar 

  • Pumplin D. W. (1989) Acetylcholine receptor clusters of rat myotubes have at least three domains with distinctive cytoskeletal and membranous components.J. Cell Biol. 109, 739–753.

    Article  PubMed  CAS  Google Scholar 

  • Pumplin D. W. and Bloch R. J. (1990) Clathrincoated membrane: a distinct membrane domain in acetylcholine receptor clusters of rat myotubes.Cell Motil. Cytoskeleton 15, 121–134.

    Article  PubMed  CAS  Google Scholar 

  • Qu Z. and Huganir R. L. (1994) Comparison of innervation and agrin-induced tyrosine phosphorylation of the nicotinic acetylcholine receptor.J. Neurosci. 14, 6834–6841.

    PubMed  CAS  Google Scholar 

  • Reist N. E., Werle M. J. and McMahan U. J. (1992) Agrin released by motor neurons induces the aggregation of acetylcholine receptors at neuromuscular junctions.Neuron 8, 865–868.

    Article  PubMed  CAS  Google Scholar 

  • Rifkin D. B. and Moscatelli D. (1989) Recent developments in the cell biology of basic fibroblast growth factor.J. Cell Biol. 109, 1–6.

    Article  PubMed  CAS  Google Scholar 

  • Robitaille R., Garcia M. I., Kaczorowski G. J., and Charlton M. P. (1993) Functional colocalization of calcium and calcium-gated potassium channels in control of neurotransmitter release.Neuron 11, 645–655.

    Article  PubMed  CAS  Google Scholar 

  • Role L. W., Matossian V. R., O'Brien R. J., and Fischbach G. D. (1985) On the mechanism of acetylcholine receptor accumulation at newly formed synapses on chick myotubes.J. Neurosci. 5, 2197–2204.

    PubMed  CAS  Google Scholar 

  • Role L. W., Roufa D. G., and Fischbach G. D. (1987) The distribution of acetylcholine receptor clusters and sites of transmitter release along chick ciliary ganglion neurite-myotube contacts in culture.J. Cell Biol. 104, 371–379.

    Article  PubMed  CAS  Google Scholar 

  • Romer L. H., Burridge K. and Turner C. E. (1992) Signaling between the extracellular matrix and the cytoskeleton: Tyrosine phosphorylation and focal adhesion assembly.Cold Spring Harbor Symp. Quant. Biol. 57, 193–202.

    PubMed  CAS  Google Scholar 

  • Ruegg M. A., Tsim K. W., Horton S. E., Kröger S., Escher G., Gensch E. M. and McMahan U. J. (1992) The agrin gene codes for a family of basal lamina proteins that differ in function and distribution.Neuron 8, 691–699.

    Article  PubMed  CAS  Google Scholar 

  • Rupp F., Payan D. G., Magill-Solc C., Cowan D. M. and Scheller R. H. (1991) Structure and expression of a rat agrin.Neuron 6, 811–823.

    Article  PubMed  CAS  Google Scholar 

  • Rupp F., Hoch W., Campanelli J. T., Kreiner T. and Scheller R. H. (1992) Agrin and the organization of the neuromuscular junction.Curr. Opinion Neurobiol. 2, 88–93.

    Article  CAS  Google Scholar 

  • Rutishauser U. (1993) Adhesion molecules of the nervous system.Curr. Opinion Neurobiol. 3, 709–715.

    Article  CAS  Google Scholar 

  • Rutishauser U., Grumet M. and Edelman G. M. (1983) Neural cell adhesion molecule mediates initial interactions between spinal cord neurons and muscle cells in culture.J. Cell Biol. 97, 145–152.

    Article  PubMed  CAS  Google Scholar 

  • Sanes J. R. (1996) The, synaptic cleft of the neuromuscular junction.Semin. Dev. Biol. 6, 163–173.

    Article  Google Scholar 

  • Sanes J. R. and Hall Z. W. (1979) Antibodies that bind specifically to synaptic sites on muscle fiber basal lamina.J. Cell Biol. 83, 357–370.

    Article  PubMed  CAS  Google Scholar 

  • Sanes J. R., Marshall L. M. and McMahan U. J. (1978) Reinnervation of muscle fiber basal lamina after removal of myofibers. Differentiation of regenerating axons at original synaptic sites.J. Cell Biol. 78, 176–198.

    Article  PubMed  CAS  Google Scholar 

  • Sanes J. R., Schachner M. and Covault J. (1986) Expression of several adhesive macromolecules (N-CAM, L1, J1, NILE, uvomorulin, laminin, fibronectin, and a heparan sulfate proteoglycan) in embryonic, adult, and denervated adult skeletal muscle.J. Cell. Biol. 102, 420–431.

    Article  PubMed  CAS  Google Scholar 

  • Sanes J. R., Engvall E., Butkowski R. and Hunter D. D. (1990) Molecular heterogeneity of basal laminae: isoforms of laminin and collagen IV at the neuromuscular junction and elsewhere.J. Cell Biol. 111, 1685–1699.

    Article  PubMed  CAS  Google Scholar 

  • Saskela O. and Rifkin D. B. (1990) Release of basic fibroblast growth factor-heparan sulfate complexes from endothelial cells by plasminogen activator-mediated proteolytic activity.J. Cell Biol. 110, 767–775.

    Article  Google Scholar 

  • Schaffner A. E. and Daniels M. P. (1982) Conditioned medium from cultures of embryonic neurons contains a high molecular weight factor which induces acetylcholine receptor aggregation on cultured myotubes.J. Neurosci. 2, 623–632.

    PubMed  CAS  Google Scholar 

  • Schecterson L. C. and Bothwell M. (1992) Novel roles for neurotrophins are suggested by BDNF and NT-3 mRNA expression in developing neurons.Neuron 9, 449–463.

    Article  PubMed  CAS  Google Scholar 

  • Schlessinger J. and Ullrich A. (1992) Growth factor signaling by receptor tyrosine kinases.Neuron 9, 383–391.

    Article  PubMed  CAS  Google Scholar 

  • Shimada Y., Fischman D. A. and Moscona A. A. (1969) Formation of neuromuscular junctions in embryonic cell cultures.Proc. Natl. Acad. Sci. USA 62, 715–721.

    Article  PubMed  CAS  Google Scholar 

  • Si J., Luo Z. and Mei L. (1996) Induction of acetylcholine receptor gene expression by ARIA requires activation of mitogen-activated protein kinase.J. Biol. Chem. 271, 19752–19759.

    Article  PubMed  CAS  Google Scholar 

  • Stone D. M. and Nikolics K. (1995) Tissue- and age-specific expression patterns of alternatively splicedagrin mRNA transcripts in embryonic rat suggest novel developmental roles.J. Neurosci. 15, 6767–6778.

    PubMed  CAS  Google Scholar 

  • Sugivama J., Bowen D. C. and Hall Z. W. (1994) Dystroglycan binds nerve and muscle agrin.Neuron. 13, 103–115.

    Article  Google Scholar 

  • Swenarchuk L. E., Champaneria S., and Anderson M. J. (1990) Induction of a specialized muscle basal lamina at chimaeric synapses in culture.Development 110, 51–61.

    PubMed  CAS  Google Scholar 

  • Swope S. L. and Huganir R. L. (1993) Molecular cloning of two abundant protein tyrosine kinases in Torpedo electric organ that associate with the acetylcholine receptor.J. Biol. Chem. 268, 25,152–25,161.

    CAS  Google Scholar 

  • Swope S. I. and Huganir, R. L. (1994) Binding of the nicotinic acetylcholine receptor to SH2 domains of Fyn and Fyk protein tyrosine kinases.J. Biol. Chem. 269, 29,817–29,824.

    CAS  Google Scholar 

  • Sytkowski A. J., Vogel Z. and Nirenberg M. W. (1973) Development of acetylcholine receptor clusters on cultured muscle cells.Proc. Natl. Acad. Sci. USA 70, 270–274.

    Article  PubMed  CAS  Google Scholar 

  • Szabat E. and Rauvala H. (1996) Role of HB-GAM (Heparin-Binding Growth-Associated Molecule) in proliferation arrest in cells of the developing rat limb and its expression in the differentiating neuromuscular system.Dev. Biol. 178, 77–89.

    Article  PubMed  CAS  Google Scholar 

  • Takahashi T., Nakajima Y., Hirosawa K., Nakajima S. and Onodera K. (1987) Structure and physiology of developing neuromuscular synapses in culture.J. Neurosci. 7, 473–481.

    PubMed  CAS  Google Scholar 

  • Takami K., Kawai Y., Shiosaka S., Lee Y., Girgis S., Hillyard C. J., MacIntyre I., Emson P. C. and Tohyama M. (1985a) Immunohistochemical evidence for the coexistence of calcitonin gene-related peptide and choline acetyltransferase-like immunoreactivity in neurons of the rat hypoglossal, facial and ambiguus nuclei.Brain Res. 328, 386–389.

    Article  PubMed  CAS  Google Scholar 

  • Takami K., Kawai Y., Uchida S., Tohyama M., Shiotani Y., Yoshida H., Emson P. C., Girgis S., Hillyard C. J. and MacIntyre I. (1985b) Effect of calcitonin gene-related peptide on contraction of striated muscle in the mouse.Neurosci. Lett. 60, 227–230.

    Article  PubMed  CAS  Google Scholar 

  • Tansey M. G., Chu G. C. and Merlie J. P. (1996) ARIA/HRG regulates AChR ε subunit gene expression at the neuromuscular synapse via activation of phosphatidylinositol 3-kinase and ras/MAPK pathway.J. Cell Biol. 134, 465–476.

    Article  PubMed  CAS  Google Scholar 

  • Tsen G., Halfter W., Kröger S. and Cole G. J. (1995) Agrin is a heparan sulfate proteoglycan.J. Biol. Chem. 270, 3392–3399.

    Article  PubMed  CAS  Google Scholar 

  • Tsim K. W. K., Ruegg M. A., Escher G., Kröger Stephan S. and McMahan U. J. (1992) cDNA that encodes active agrin.Neuron 8, 677–689.

    Article  PubMed  CAS  Google Scholar 

  • Uchida S., Yamamoto H., Iio S., Matsumoto N., Wang X.-B., Yonehara N., Imai Y., Inoki R. and Yoshida H. (1990) Release of calcitonin generelated peptide-like immunoreactive substance from neuromuscular junction by nerve excitation and its action on striated muscle.J. Neurochem. 54, 1000–1003.

    Article  PubMed  CAS  Google Scholar 

  • Usdin T. B. and Fischbach G. D. (1986) Purification and characterization of a polypeptide from chick brain that promotes the accumulation of acetylcholine receptors in chick myotubes.J. Cell Biol. 103, 493–507.

    Article  PubMed  CAS  Google Scholar 

  • Vactor D. V., Sink H., Fambrough D., Tsoo R., and Goodman C. S. (1993) Genes that control neuromuscular specificity in Drosophila.Cell 73, 1137–1153.

    Article  PubMed  CAS  Google Scholar 

  • Valenzuela D. M., Stitt T. N., DiStefano P. S., Rojas E., Mattsson K., Compton D. L., Nunez I., Park J. S., Stark J. L., Gies D. R. et al. (1995) Receptor tyrosine kinase specific for the skeletal muscle lineage: expression in embryonic muscle, at the neuromuscular junction, and after injury.Neuron 15, 573–584.

    Article  PubMed  CAS  Google Scholar 

  • Vogel Z., Sytkowski A. J. and Nirenberg M. W. (1972) Acetylcholine receptors of muscle grown in vitro.Proc. Natl. Acad. Sci. USA 69, 3180–3184.

    Article  PubMed  CAS  Google Scholar 

  • Vogel Z., Daniels M. P., Chen T., Xi Z. Y., Bachar E., Ben-David L., Rosenberg N., Krause M., Duksin D. and Kalcheim C. (1987) Ascorbate-like factor from embryonic brain. Role in collagen formation, basement membrane deposition, and acetylcholine receptor aggregation by muscle cells.Ann. NY Acad. Sci. 498, 13–27.

    Article  PubMed  CAS  Google Scholar 

  • Wagner K. R., Cohen J. B. and Huganir R. L. (1993) The 87K postsynaptic membrane protein from Torpedo is a protein-tyrosine kinase substrate homologous, to dystrophin.Neuron 10, 511–522.

    Article  PubMed  CAS  Google Scholar 

  • Wallace B. G. (1988) Regulation of agrin-induced acetylcholine receptor aggregation by Ca++ and phorbol ester.J. Cell Biol. 107, 267–278.

    Article  PubMed  CAS  Google Scholar 

  • Wallace B. G., Qu Z., and Huganir R. L. (1991) Agrin induces phosphorylation of the nicotinic acetylcholine receptor.Neuron 6, 869–878.

    Article  PubMed  CAS  Google Scholar 

  • Wallace B. G. (1994) Staurosporine inhibits agrin-induced acetylcholine receptor phosphorylation and aggregation.J. Cell Biol. 125, 661–668.

    Article  PubMed  CAS  Google Scholar 

  • Wallace B. G. (1995) Regulation of the interaction of nicotinic acetylcholine receptors with the cytoskeleton by agrin-activated protein tyrosine kinase.J. Cell Biol. 128, 1121–1129.

    Article  PubMed  CAS  Google Scholar 

  • Wang T., Xie K. and Lu B. (1995) Neurotrophins promote maturation of developing neuromuscular synapses.J. Neurosci. 15, 4796–4805.

    PubMed  CAS  Google Scholar 

  • Wen D., Peles E., Cupples R., Suggs S. V., Bacus S. S., Luo Y., Trail G., Hu S., Silbiger S. M., Ben-Levy R. and Yarden Y. (1992) Neu differentiation factor: A transmembrane glycoprotein containing an EGF domain and an immunoglobulin homology unit.Cell 69, 559–572.

    Article  PubMed  CAS  Google Scholar 

  • Werle M. J. and McMahan U. J. (1991) Molecules that induce the formation of synaptic apparatus, inPlasticity of motoneuronal connections (Wernig A. ed.), Elsevier, New York, p. 269.

    Google Scholar 

  • Williams E. J., Furness J., Walsh F. S., and Doherty P. (1994) Activation of the FGF receptor underlies neurite outgrowth stimulated by L1, N-CAM, and N-cadherin.Neuron 13, 583–594.

    Article  PubMed  CAS  Google Scholar 

  • Xie Z. P. and Poo M. M. (1986) Initial events in the formation of neuromuscular synapse: rapid induction of acetylcholine release from embryonic neurons.Proc. Natl. Acad. Sci. USA 83, 7069–7073.

    Article  PubMed  CAS  Google Scholar 

  • Young S. H. and Poo M. M. (1983) Spontaneous release of transmitter from growth cones of embryonic neurones.Nature 305, 634–637.

    Article  PubMed  CAS  Google Scholar 

  • Zoran M. J., Doyle R. T. and Haydon P. G. (1990) Target-dependent induction of secretory capabilities in an, identified motoneuron during synaptogenesis.Dev. Biol. 138, 202–213.

    Article  PubMed  CAS  Google Scholar 

  • Zoran M. J., Doyle R. T. and Haydon P. G. (1991) Target contact regulates the calcium responsiveness of the secretory machinery during synaptogenesis.Neuron 6, 145–151.

    Article  PubMed  CAS  Google Scholar 

  • Zoran M. J., Funte L. R., Kater S. B. and Haydon P. G. (1993) Neuron-muscle contact changes presynaptic resting calcium set-point.Dev. Biol. 158, 163–171.

    Article  PubMed  CAS  Google Scholar 

  • Zoubine M. N., Ma J. Y., Smirnova I. V., Citron B. A. and Festoff B. W. (1996) A molecular mechanism for synapse elimination: novel inhibition of locally generated thrombin delays synapse loss in neonatal mouse muscle.Dev. Biol. 179, 447–457.

    Article  PubMed  CAS  Google Scholar 

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Daniels, M.P. Intercellular communication that mediates formation of the neuromuscular junction. Mol Neurobiol 14, 143–170 (1997). https://doi.org/10.1007/BF02740654

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