Gradual loss of synaptic cartels precedes axon withdrawal at developing neuromuscular junctions

Balice-Gordon, Rita J.; Chua, Christine K.; Nelson, Carla C.; Lichtman, Jeff W.

doi:10.1016/0896-6273(93)90110-d

Cited by 114 publications

(59 citation statements)

References 21 publications

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“…3). These types of structure are associated with axon retraction in vertebrates (Balice-Gordon et al, 1993;Gan and Lichtman, 1998). In association with these structures, we also observed mRFP-positive (and sometimes GFP::RAB-3-positive) spherical 'remnants' in positions where mature synapses usually reside (Fig.…”

Section: Zyx-1 Plm Synaptic Varicosities Are Unstablementioning

confidence: 70%

The conserved LIM domain-containing focal adhesion protein ZYX-1 regulates synapse maintenance inCaenorhabditis elegans

et al. 2014

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We describe the identification of zyxin as a regulator of synapse maintenance in mechanosensory neurons in C. elegans. zyx-1 mutants lacked PLM mechanosensory synapses as adult animals. However, most PLM synapses initially formed during development but were subsequently lost as the animals developed. Vertebrate zyxin regulates cytoskeletal responses to mechanical stress in culture. Our work provides in vivo evidence in support of such a role for zyxin. In particular, zyx-1 mutant synaptogenesis phenotypes were suppressed by disrupting locomotion of the mutant animals, suggesting that zyx-1 protects mechanosensory synapses from locomotion-induced forces. In cultured cells, zyxin is recruited to focal adhesions and stress fibers via C-terminal LIM domains and modulates cytoskeletal organization via the N-terminal domain. The synapse-stabilizing activity was mediated by a short isoform of ZYX-1 containing only the LIM domains. Consistent with this notion, PLM synaptogenesis was independent of α-actinin and ENA-VASP, both of which bind to the N-terminal domain of zyxin. Our results demonstrate that the LIM domain moiety of zyxin functions autonomously to mediate responses to mechanical stress and provide in vivo evidence for a role of zyxin in neuronal development.

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Section: Zyx-1 Plm Synaptic Varicosities Are Unstablementioning

confidence: 70%

The conserved LIM domain-containing focal adhesion protein ZYX-1 regulates synapse maintenance inCaenorhabditis elegans

et al. 2014

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“…Twenty-five percent of the NMJs in P15 P 0 tg gluteus maximus were partially denervated (Table 1). The preterminal axons, however, did not degenerate or form axonal retraction bulbs, the stereotypic appearance of preterminal axonal withdrawal at NMJs (Balice-Gordon et al, 1993). On the basis of these observations, NMJs in P 0 tg mice form normally during development.…”

Section: Neurological Disability Correlates With Muscle Fibrillation mentioning

confidence: 74%

Dysmyelinated Lower Motor Neurons Retract and Regenerate Dysfunctional Synaptic Terminals

et al. 2004

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Axonal degeneration is the major cause of permanent neurological disability in individuals with inherited diseases of myelin. Axonal and neuronal changes that precede axonal degeneration, however, are not well characterized. We show here that dysmyelinated lower motor neurons retract and regenerate dysfunctional presynaptic terminals, leading to severe neurological disability before axonal degeneration. In addition, dysmyelination led to a decreased synaptic quantal content, an indicator of synaptic dysfunction. The amplitude and rise time of miniature endplate potentials were also increased, but these changes were primarily consistent with an increase in the passive membrane properties of the transgenic muscle fibers. Maintenance of synaptic connections should be considered as a therapeutic target for slowing progression of neurological disability in primary diseases of myelin.

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“…Motor axons lose branches asynchronously and without spatial bias (28), suggesting that local interactions at each NMJ regulate synapse elimination. Synapse elimination at the NMJ is an activity-dependent process, where weakening of synaptic function is thought to precede synapse dismantling (29)(30)(31). Evidence from both the mammalian and Drosophila NMJ indicates that presynaptic disassembly precedes disassembly of the postsynaptic apparatus upon synapse destabilization (28,32).…”

Section: Synaptogenesis: a Microscopic Viewmentioning

confidence: 99%

The Developing Synapse: Construction and Modulation of Synaptic Structures and Circuits

Cohen-Cory

2002

Science

410

268

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Synapse formation and stabilization in the vertebrate central nervous system is a dynamic process, requiring bi-directional communication between pre-and postsynaptic partners. Numerous mechanisms coordinate where and when synapses are made in the developing brain. This review discusses cellular and activity-dependent mechanisms that control the development of synaptic connectivity.The function of the nervous system critically relies on the establishment of precise synaptic connections between neurons and specific target cells (Fig. 1). During synaptogenesis, synapses form, mature, and stabilize and are also eliminated by a process that requires intimate communication between pre-and postsynaptic partners. Most of our understanding of synapse formation and stabilization comes from extensive studies performed at the neuromuscular junction (NMJ). However, recent advances in methodologies that include real-time imaging of living neurons have provided insight into the molecular, cellular, and activity-dependent processes that guide synaptogenesis in the developing central nervous system (CNS). This review highlights several aspects of vertebrate synaptogenesis and its relation to activity-dependent processes, from the cellular mechanisms by which neurons communicate with each other to establish synaptic contacts to the role of activity during the development of topographically ordered neuronal maps. Emphasis is placed on the development of central excitatory synapses, and some aspects of NMJ development are also discussed. Synaptogenesis: A Microscopic ViewIn the CNS, synapse assembly begins when axons approach their targets and establish contact with dendritic arbors or soma of their target neurons. Real-time imaging experiments demonstrate that both axonal and dendritic filopodia actively participate in synapse formation (Fig. 2). Highly dynamic interactions at contact sites of advancing axon growth cones and dendritic filopodia have been demonstrated in living zebrafish embryos in which pre-and postsynaptic partners were labeled with green fluorescent protein (GFP) (1). Highly motile dendritic filopodia in zebrafish embryos resemble those of mammalian developing central neurons undergoing synaptogenesis both in culture (2, 3) and in vivo (4). Dynamic filopodia are also present in developing axon arbors before synapse differentiation (5-8) and have been implicated in synapse formation (9). Real-time imaging of GFP-labeled synaptic components and functional imaging of presynaptic sites (labeled with FM 1-43, a vital dye that reveals activityevoked synaptic vesicle recycling) have revealed the time course and sequence of events in CNS synaptogenesis. Imaging GFP-tagged synaptobrevin II (also known as VAMP II, a synaptic vesicle protein) in cultured hippocampal neurons revealed that transport packets containing preassembled synaptic vesicle components begin to accumulate at presynaptic sites immediately after axons and dendritic filopodia establish initial contact (10). Presynaptic components are assembled very rapi...

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Gradual loss of synaptic cartels precedes axon withdrawal at developing neuromuscular junctions

Cited by 114 publications

References 21 publications

The conserved LIM domain-containing focal adhesion protein ZYX-1 regulates synapse maintenance inCaenorhabditis elegans

The conserved LIM domain-containing focal adhesion protein ZYX-1 regulates synapse maintenance inCaenorhabditis elegans

Dysmyelinated Lower Motor Neurons Retract and Regenerate Dysfunctional Synaptic Terminals

The Developing Synapse: Construction and Modulation of Synaptic Structures and Circuits

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