Axonal guidance and the development of muscle fiber-specific innervation in Drosophila embryos

Abstract

The outgrowth of peripheral nerves and the development of muscle fiber-specific neuromuscular junctions were examined in Drosophila embryos using immunocytochemistry and computer-enhanced digital optical microscopy. We find that the pioneering of the peripheral nerves and the formation of the neuromuscular junctions occur through a precisely orchestrated sequence of stereotyped axonal trajectories, mediated by the selective growth cone choices of pioneer motoneurons. We have also examined the establishment of the embryonic muscle fibers and, using intracellular dye fills, have identified cells that are putative muscle pioneers. The muscle fibers of the bodywall have completed their morphogenesis prior to the initiation of synaptic contacts, and owing to the timing of neurite outgrowth from the CNS, synaptogenesis is synchronous at muscle fibers throughout the bodywall. At each muscle fiber the innervating axons make their initial contacts on a characteristic surface domain of the target cell's membrane. Through stereotyped growth cone-mediated trajectories the motoneurons actively establish the basic anatomical features of the mature neuromuscular junction, including the stereotyped, muscle fiber-specific branch anatomy. These events occur without significant process pruning or apparent synapse elimination. Our results suggest that the basic elements of the mature neuromuscular innervation, including the details of the ending trajectory on the target cell's surface, are formed by the precise navigation and presumed recognition by the motoneuron growth cones of muscle membrane surface features.

Crk-associated substrate (Cas) signaling protein functions with integrins to specify axon guidance during development

“…This in vitro observation resembles in vivo situations in which growth cones slow at a choice point, exhibit increased morphological complexity and then extend along distinct pathways (Godement et al, 1994;Gomez and Spitzer, 1999;Tosney and Landmesser, 1985). Drosophila motor axon growth cones also exhibit similar changes in morphological complexity upon contacting different substrates in vivo, suggesting that similar processes function to generate motor axon trajectories (Broadie et al, 1993;Johansen et al, 1989;Sink and Whitington, 1991). Different combinations of integrin ligands might be responsible for these effects.…”

Cell Type-Specific Requirements for Heparan Sulfate Biosynthesis at the Drosophila Neuromuscular Junction: Effects on Synapse Function, Membrane Trafficking, and Mitochondrial Localization

“…1 A, asterisk). Muscles 6 and 7 are innervated by two motoneurons that both use glutamate as the neurotransmitter (Johansen et al, 1989). One motoneuron forms larger type Ib boutons on muscles 6 and 7, whereas the other makes smaller type Is boutons on these and several adjacent muscles (Hoang and Chiba, 2001).…”

Ultrastructure of neuromuscular junctions in Drosophilal: Comparison of wild type and mutants with increased excitability

“…It is, therefore, likely that synapses are also continuously forming during development to keep pace with enlarging boutons. The expansion of neuromuscular junctions may be a mechanism to match the growth of muscles that occurs during the larval period (Johansen et al, 1989b;Gorczyca et al, 1993). It is possible that neuronal activity is involved in this phenomenon, because in eag Sh mutants there is an increase in the number of synaptic boutons (Budnik et al, 1990).…”

“…The most characterized of these transmitters is glutamate, which, as in most invertebrate neuromuscular junctions, is believed to be the main excitatory transmitter (Jan and Jan, 1976b;Johansen et al, 1989a;Broadie and Bate, 1993). Immunocytochemical studies indicate that this transmitter is ubiquitously expressed at synaptic terminals that innervate all body wall muscles (Johansen, 1989b). The presence of other putative neurotransmitters or neuromodulators such as proctolin , octopamine , leucokinin I (Cantera and Nässel, 1992), and insulin (Gorczyca, Augart, and Budnik, 1993) has been demonstrated by immunocytochemical and/or biochemical techniques.…”