Activity-dependent development of the neuromuscular synapse during drosophila embryogenesis

In Drosophila, mutations in specific ion channel genes can increase or decrease the level of neural/synaptic activity. We have used these genetic tools, in combination with classical pharmacological agents, to modulate neural activity during embryogenesis and examined effects on the differentiation of an identified neuromuscular junction. We find that electrical activity is required for the neural induction of transmitter receptor expression during synaptogenesis. Likewise, neural electrical activity is required to localize transmitter receptors to the synaptic site. In muscles with activity-blocked synapses, a low level of receptors is expressed homogeneously in the muscle membrane as in muscles developing without innervation. Thus, presynaptic electrical activity is required to mediate the neural induction of the transmitter receptor field in the postsynaptic membrane.

[1]  M. Bate,et al.  Development of the embryonic neuromuscular synapse of Drosophila melanogaster , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[2]  Y. Jan,et al.  Antibodies to horseradish peroxidase as specific neuronal markers in Drosophila and in grasshopper embryos. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[3]  M. Anderson,et al.  Effects of innervation on the distribution of acetylcholine receptors on cultured muscle cells. , 1977, The Journal of physiology.

[4]  Y. Zhong,et al.  Synaptic plasticity in Drosophila memory and hyperexcitable mutants: role of cAMP cascade , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[5]  Y. Zhong,et al.  Altered synaptic plasticity in Drosophila memory mutants with a defective cyclic AMP cascade. , 1991, Science.

[6]  J. Fallon,et al.  Agrin and the molecular choreography of synapse formation , 1993, Trends in Neurosciences.

[7]  Miriam M. Salpeter,et al.  Nicotinic acetylcholine receptors in vertebrate muscle: Properties, distribution and neural control , 1985, Progress in Neurobiology.

[8]  A. Harris Embryonic growth and innervation of rat skeletal muscles. III. Neural regulation of junctional and extra-junctional acetylcholine receptor clusters. , 1981, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[9]  C. Wu,et al.  Voltage clamp analysis of membrane currents in larval muscle fibers of Drosophila: alteration of potassium currents in Shaker mutants , 1985, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[10]  B. Ganetzky,et al.  Drosophila mutants with opposing effects on nerve excitability: genetic and spatial interactions in repetitive firing. , 1982, Journal of neurophysiology.

[11]  O. Pongs,et al.  Molecular organization of the maternal effect region of the Shaker complex of Drosophila: characterization of an IA channel transcript with homology to vertebrate Na+ channel , 1987, The EMBO journal.

[12]  G. Lnenicka,et al.  The refinement of invertebrate synapses during development. , 1989, Journal of neurobiology.

[13]  H. Sink,et al.  Pathfinding in the central nervous system and periphery by identified embryonic Drosophila motor axons. , 1991, Development.

[14]  W. D. Kaplan,et al.  The behavior of four neurological mutants of Drosophila. , 1969, Genetics.

[15]  R. Drysdale,et al.  A distinct potassium channel polypeptide encoded by the Drosophila eag locus , 1991, Science.

[16]  M. Westerfield,et al.  Clustering of muscle acetylcholine receptors requires motoneurons in live embryos, but not in cell culture , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[17]  W. D. Phillips,et al.  Recombinant neuromuscular synapses , 1992, BioEssays : news and reviews in molecular, cellular and developmental biology.

[18]  M. Bate,et al.  The embryonic development of larval muscles in Drosophila. , 1990, Development.

[19]  C. Shatz,et al.  Developmental mechanisms that generate precise patterns of neuronal connectivity , 1993, Cell.

[20]  M. Poo,et al.  Studies of nerve-muscle interactions in Xenopus cell culture: analysis of early synaptic currents , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[21]  R. Aldrich,et al.  Alterations in the expression and gating of drosophila sodium channels by mutations in the para gene , 1989, Neuron.

[22]  R. Drysdale,et al.  Molecular characterization of eag: a gene affecting potassium channels in Drosophila melanogaster. , 1991, Genetics.

[23]  Y. Jan,et al.  Two Mutations of synaptic transmission in Drosophila , 1977, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[24]  B. Ganetzky,et al.  Neurogenetic analysis of potassium currents in Drosophila: synergistic effects on neuromuscular transmission in double mutants. , 1983, Journal of neurogenetics.

[25]  B. Ganetzky,et al.  Neurogenetics of membrane excitability in Drosophila. , 1986, Annual review of genetics.

[26]  B. Sakmann,et al.  Neural factors regulate AChR subunit mRNAs at rat neuromuscular synapses , 1991, The Journal of cell biology.

[27]  Y. Jan,et al.  Sequence of a probable potassium channel component encoded at Shaker locus of Drosophila. , 1987, Science.

[28]  LM Dahm,et al.  The regulation of synaptogenesis during normal development and following activity blockade , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[29]  Y. Jan,et al.  L‐glutamate as an excitatory transmitter at the Drosophila larval neuromuscular junction. , 1976, The Journal of physiology.

[30]  S. Heinemann,et al.  Acetylcholine receptor α-, β-, γ-, and δ-subunit mRNA levels are regulated by muscle activity , 1988, Neuron.

[31]  H. Keshishian,et al.  Stereotypic morphology of glutamatergic synapses on identified muscle cells of Drosophila larvae , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[32]  W. Harris Neural activity and development. , 1981, Annual review of physiology.

[33]  M. Bate,et al.  Innervation directs receptor synthesis and localization in Drosophila embryo synaptogenesis , 1993, Nature.

[34]  M. Westerfield,et al.  Pathfinding and synapse formation in a zebrafish mutant lacking functional acetylcholine receptors , 1990, Neuron.

[35]  D. Suzuki,et al.  Temperature-sensitive mutations in Drosophila melanogaster. VII. A mutation (para-ts) causing reversible adult paralysis. , 1971, Proceedings of the National Academy of Sciences of the United States of America.

[36]  Y. Zhong,et al.  Morphological plasticity of motor axons in Drosophila mutants with altered excitability , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[37]  M. Tanouye,et al.  Action potentials in normal and Shaker mutant Drosophila. , 1985, Journal of neurogenetics.

[38]  B. Ganetzky,et al.  Genetic alteration of nerve membrane excitability in temperature-sensitive paralytic mutants of Drosophila melanogaster , 1980, Nature.

[39]  M. Bate,et al.  Development of larval muscle properties in the embryonic myotubes of Drosophila melanogaster , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[40]  L. Salkoff,et al.  Genomic organization and deduced amino acid sequence of a putative sodium channel gene in Drosophila. , 1987, Science.

[41]  Y. Jan,et al.  Cloning of genomic and complementary DNA from Shaker, a putative potassium channel gene from Drosophila. , 1987, Science.

[42]  H. Keshishian,et al.  Growth cone behavior underlying the development of stereotypic synaptic connections in Drosophila embryos , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[43]  M. Tanouye,et al.  Molecular characterization of Shaker, a Drosophila gene that encodes a potassium channel , 1987, Cell.

[44]  S. Cash,et al.  Alternate neuromuscular target selection following the loss of single muscle fibers in Drosophila , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[45]  J. Sanes,et al.  Synaptic structure and development: The neuromuscular junction , 1993, Cell.

[46]  J. Bessereau,et al.  Compartmentalization of acetylcholine receptor gene expression during development of the neuromuscular junction. , 1990, Cold Spring Harbor symposia on quantitative biology.

[47]  B. Ganetzky,et al.  Molecular analysis of the para locus, a sodium channel gene in Drosophila , 1989, Cell.

[48]  B. Ganetzky,et al.  Potassium currents in Drosophila: different components affected by mutations of two genes. , 1983, Science.

[49]  L. Patthy,et al.  Functions of agrin and agrin-related proteins , 1993, Trends in Neurosciences.

[50]  R. Eftimie,et al.  Myogenin and MyoD join a family of skeletal muscle genes regulated by electrical activity. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[51]  C. Goodman,et al.  Genes that control neuromuscular specificity in Drosophila , 1993, Cell.