Neuromuscular blockade increases motoneurone survival during normal cell death in the chick embryo

Pittman, Randall; Oppenheim, Ronald W.

doi:10.1038/271364a0

Cited by 240 publications

(67 citation statements)

References 17 publications

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“…In the Munc18-1 mutant embryos, AChRs are clustered as well, although the ultrastructure of their synapses has not been reported. Our findings of increased muscle innervation and motor neuron survival are also consistent with previous studies using cholinergic or neuromuscular activity blockers in chick embryos (Pittman and Oppenheim, 1978;Landmesser, 1988, 1991;Oppenheim et al, 1989Oppenheim et al, , 2000Hory-Lee and Frank, 1995;Usiak and Landmesser, 1999).…”

Section: Discussionsupporting

confidence: 82%

“…Similar results were observed in E18.5 limb and intercostal muscles (data not shown). These results are consistent with previous studies in chick embryos treated with AChR antagonists (Burden, 1977;Pittman and Oppenheim, 1978;Srihari and Vrbova, 1978;Landmesser, 1988, 1991;Oppenheim et al, 1989Oppenheim et al, , 2000Hory-Lee and Frank, 1995;Usiak and Landmesser, 1999). To determine whether Schwann cells are present in Chat mutants, we examined the distribution of Schwann cells in motor nerves.…”

Section: Increased Innervation and Spinal Motor Neuron Survivalsupporting

confidence: 80%

“…In light of increased muscle innervation, we sought to determine whether motor neuron survival is affected in ChAT mutants. Consistent with previous studies using ACh antagonists with chicks in ovo (Pittman and Oppenheim, 1978;Srihari and Vrbova, 1978;Landmesser, 1988, 1991;Oppenheim et al, 1989Oppenheim et al, , 2000Hory-Lee and Frank, 1995;Usiak and Landmesser, 1999), homozygous Chat mutant embryos were found to have ϳ60% more motor neurons in cervical and thoracic segments than control embryos (Fig. 3G).…”

Section: Increased Innervation and Spinal Motor Neuron Survivalsupporting

confidence: 80%

“…Several investigators have used the application of AChR antagonists such as d-turbocurare (dTC) to chicks in ovo (Burden, 1977;Pittman and Oppenheim, 1978;Srihari and Vrbova, 1978;Landmesser, 1988, 1991;Oppenheim et al, 1989Oppenheim et al, , 2000Hory-Lee and Frank, 1995;Usiak and Landmesser, 1999), an approach that has proved to be very informative. However, the analogous in utero pharmacological interventions in rodents have been of limited use because at stages before nerve-muscle contact, the manipulations have dire effects on the pregnant mother and/or developing fetuses (Braithwaite and Harris, 1979;Houenou et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

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Aberrant Patterning of Neuromuscular Synapses in Choline Acetyltransferase-Deficient Mice

et al. 2003

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In this study we examined the developmental roles of acetylcholine (ACh) by establishing and analyzing mice lacking choline acetyltransferase (ChAT), the biosynthetic enzyme for ACh. As predicted, ChAT-deficient embryos lack both spontaneous and nerve-evoked postsynaptic potentials in muscle and die at birth. In mutant embryos, abnormally increased nerve branching occurs on contact with muscle, and hyperinnervation continues throughout subsequent prenatal development. Postsynaptically, ACh receptor clusters are markedly increased in number and occupy a broader muscle territory in the mutants. Concomitantly, the mutants have significantly more motor neurons than normal. At an ultrastructural level, nerve terminals are smaller in mutant neuromuscular junctions, and they make fewer synaptic contacts to the postsynaptic muscle membrane, although all of the typical synaptic components are present in the mutant. These results indicate that ChAT is uniquely essential for the patterning and formation of mammalian neuromuscular synapses.

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Section: Discussionsupporting

confidence: 82%

Section: Increased Innervation and Spinal Motor Neuron Survivalsupporting

confidence: 80%

Section: Increased Innervation and Spinal Motor Neuron Survivalsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

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Aberrant Patterning of Neuromuscular Synapses in Choline Acetyltransferase-Deficient Mice

et al. 2003

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“…For example, the neurotransmitter acetylcholine (ACh) is released from embryonic motor neurons (MNs) at the neuromuscular junction (NMJ), and it negatively regulates survival, axon branching, and synapse formation (4)(5)(6)(7). ACh is also released from developing neurons even before they arrive at their target, and it acts in an autocrine and/or paracrine fashion to regulate growth (8), pathfinding (9), spontaneous activity (10), and target selection (11).…”

mentioning

confidence: 99%

Acetylcholine negatively regulates development of the neuromuscular junction through distinct cellular mechanisms

Lin²,

Yang

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Emerging evidence suggests that the neurotransmitter acetylcholine (ACh) negatively regulates the development of the neuromuscular junction, but it is not clear if ACh exerts its effects exclusively through muscle ACh receptors (AChRs). Here, we used genetic methods to remove AChRs selectively from muscle. Similar to the effects of blocking ACh biosynthesis, eliminating postsynaptic AChRs increased motor axon branching and expanded innervation territory, suggesting that ACh negatively regulates synaptic growth through postsynaptic AChRs. However, in contrast to the effects of blocking ACh biosynthesis, eliminating postsynaptic AChRs in agrin-deficient mice failed to restore deficits in pre- and postsynaptic differentiation, suggesting that ACh negatively regulates synaptic differentiation through nonpostsynaptic receptors. Consistent with this idea, the ACh agonist carbachol inhibited presynaptic specialization of motorneurons in vitro. Together, these data suggest that ACh negatively regulates axon growth and presynaptic specialization at the neuromuscular junction through distinct cellular mechanisms.

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Late-Convalescent Poliomyelitis

Fishman¹

1987

Arch Neurol

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Neuromuscular blockade increases motoneurone survival during normal cell death in the chick embryo

Cited by 240 publications

References 17 publications

Aberrant Patterning of Neuromuscular Synapses in Choline Acetyltransferase-Deficient Mice

Aberrant Patterning of Neuromuscular Synapses in Choline Acetyltransferase-Deficient Mice

Acetylcholine negatively regulates development of the neuromuscular junction through distinct cellular mechanisms

Late-Convalescent Poliomyelitis

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