Pathway selection by growth cones of identified motoneurones in live zebra fish embryos

Eisen, Judith S; Myers, Paul Z.; Westerfield, Monte

doi:10.1038/320269a0

Cited by 324 publications

(200 citation statements)

References 15 publications

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“…Our work is based on the pioneering studies of Eisen, Westerfield and colleagues (Eisen and Meyers, 1986;Meyers et al, 1986Fashena and Westerfield, 1999;Westerfield et al, 1990;Sepich et al, 1998;Liu and Westerfield, 1992). In general, our results are consistent with theirs, but they differ in one respect: they did not observe aneural AChR clusters prior to axon outgrowth or in segments rendered aneural by the ablation of primary motoneurons (Liu and Westerfield, 1992).…”

Section: Discussionsupporting

confidence: 79%

Neuromuscular synapses can form in vivo by incorporation of initially aneural postsynaptic specializations

et al. 2005

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Synapse formation requires the coordination of pre- and postsynaptic differentiation. An unresolved question is which steps in the process require interactions between pre- and postsynaptic cells, and which proceed cell-autonomously. One current model is that factors released from presynaptic axons organize postsynaptic differentiation directly beneath the nerve terminal. Here, we used neuromuscular junctions (NMJs) of the zebrafish primary motor system to test this model. Clusters of neurotransmitter(acetylcholine) receptors (AChRs) formed in the central region of the myotome,destined to be synapse-rich, before axons extended and even when axon extension was prevented. Time-lapse imaging revealed that pre-existing clusters on early-born slow (adaxial) muscle fibers were incorporated into NMJs as axons advanced. Axons were, however, required for the subsequent remodeling and selective stabilization of synaptic clusters that precisely appose post- to presynaptic elements. Thus, motor axons are dispensable for the initial stages of postsynaptic differentiation but are required for later stages. Moreover, many AChR clusters on later-born fast muscle fibers formed at sites that had already been contacted by axons, suggesting heterogeneity in the signaling mechanisms leading to synapse formation by a single axon.

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Section: Discussionsupporting

confidence: 79%

Neuromuscular synapses can form in vivo by incorporation of initially aneural postsynaptic specializations

et al. 2005

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“…By the 14-somite stage (16 hpf), the ventrally located ret1-expressing cells were arranged in a segmental pattern relative to the borders of hemisegments 8 to 20 (2 to 3 ret1 positive cells per hemisegment; Figure 4c). These cells were likely to be primary motor neurons as indicated by their early appearance, ventrolateral location and the relatively large size of their cell bodies (Figure 4b and c; Eisen et al, 1986;Myers et al, 1986;Eisen, 1991). Vital dye labelling and immunohistochemistry using several neuron-speci®c markers, has indicated that three primary motor neurons are present in each hemisegment: the CaP, (Caudal Primary, caudally located); RoP, (Rostral Primary, rostrally located) and MiP, (Middle Primary, between CaP and RoP).…”

Section: Mrna Distribution In the Developing Excretory Systemmentioning

confidence: 99%

The zebrafish homologue of the ret receptor and its pattern of expression during embryogenesis

et al. 1997

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The c-ret proto-oncogene, a member of the receptor tyrosine kinase gene superfamily, plays a critical role in the development of the excretory system and the enteric and autonomic nervous systems of mammalian embryos. To study the potential function of the c-ret locus in lower vertebrates, we have isolated its zebra®sh homologue, ret1 and established its expression pattern during embryogenesis. Ret1 mRNA ®rst appears during early somitogenesis in the presumptive brain, spinal cord and excretory system. Within the CNS, expression of ret1 is detected in primary motor and sensory (Rohon ± Beard) neurons. Ret1 transcripts are also expressed in subsets of neural crest cells and cranial ganglia as well as in the enteric nervous system. In the excretory system, expression is detected in the developing nephric duct and the pronephros. Our ®ndings reveal a remarkable similarity in the expression pattern of c-ret between higher and lower vertebrates, suggesting that the function of this locus has been conserved throughout vertebrate evolution. Furthermore, the conservation of ret1 expression in cell types which remain una ected by the mammalian c-ret mutations, such as motor and sensory neurons, suggests a function of this receptor in these cell lineages.

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“…At 17 hpf, the first wild-type motor growth cones have exited the spinal cord and pioneer a path along the medial surface of the myotome (Bernhardt et al, 1998;Eisen et al, 1986). As pioneering growth cones advance, dense AChR clusters emerge and co-localize along the extending axon, reminiscent of en passant synapses (Fig.…”

Section: Twister-related Phenotypes Are Dependent On Neuromuscular Acmentioning

confidence: 99%

Increased neuromuscular activity causes axonal defects and muscular degeneration

et al. 2004

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Before establishing terminal synapses with their final muscle targets,migrating motor axons form en passant synaptic contacts with myotomal muscle. Whereas signaling through terminal synapses has been shown to play important roles in pre- and postsynaptic development, little is known about the function of these early en passant synaptic contacts. Here, we show that increased neuromuscular activity through en passant synaptic contacts affects pre- and postsynaptic development. We demonstrate that in zebrafish twistermutants, prolonged neuromuscular transmission causes motor axonal extension and muscular degeneration in a dose-dependent manner. Cloning of twister reveals a novel, dominant gain-of-function mutation in the muscle-specific nicotinic acetylcholine receptor α-subunit, CHRNA1. Moreover, electrophysiological analysis demonstrates that the mutant subunit increases synaptic decay times, thereby prolonging postsynaptic activity. We show that as the first en passant synaptic contacts form, excessive postsynaptic activity in homozygous embryos severely impedes pre- and postsynaptic development, leading to degenerative defects characteristic of the human slow-channel congenital myasthenic syndrome. By contrast, in heterozygous embryos, transient and mild increase in postsynaptic activity does not overtly affect postsynaptic morphology but causes transient axonal defects, suggesting bi-directional communication between motor axons and myotomal muscle. Together, our results provide compelling evidence that during pathfinding, myotomal muscle cells communicate extensively with extending motor axons through en passant synaptic contacts.

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Pathway selection by growth cones of identified motoneurones in live zebra fish embryos

Cited by 324 publications

References 15 publications

Neuromuscular synapses can form in vivo by incorporation of initially aneural postsynaptic specializations

Neuromuscular synapses can form in vivo by incorporation of initially aneural postsynaptic specializations

The zebrafish homologue of the ret receptor and its pattern of expression during embryogenesis

Increased neuromuscular activity causes axonal defects and muscular degeneration

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