DNA Topoisomerase IIβ and Neural Development

Yang, Xia; Li, Wei; Prescott, Elizabeth D.; Burden, Steven; Wang, James C.

doi:10.1126/science.287.5450.131

Cited by 323 publications

(273 citation statements)

References 26 publications

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“…Recent studies have demonstrated that muscle is pre-specialized in the central, prospective synaptic region prior to and independent of innervation, and these findings have led to a revised view of the steps and mechanisms that regulate neuromuscular synapse formation (Flanagan-Steet et al, 2005;Lin et al, 2001;Panzer et al, 2006;Yang et al, 2001;Yang et al, 2000). Key features of postsynaptic differentiation are established in a muscleautonomous, MuSK-dependent manner and motor neurons refine and sharpen, rather than induce this prepattern of postsynaptic differentiation.…”

Section: Discussionmentioning

confidence: 99%

“…AChR gene expression and AChR clusters are concentrated in the central region of skeletal muscle in the absence of innervation (Lin et al, 2001;Yang et al, 2001;Yang et al, 2000). This nerve-independent patterning of AChR expression, termed muscle prepatterning, is dependent upon MuSK (Lin et al, 2001;Yang et al, 2001), a receptor tyrosine kinase that is activated by Agrin and essential for neuromuscular synapse formation (DeChiara et al, 1996;Strochlic et al, 2005).…”

Section: Musk Expression Is Patterned In Muscle Lacking Motor Axonsmentioning

confidence: 99%

“…We next sought to determine how MuSK prepatterning is established. Previously, we raised the possibility that the temporal pattern of muscle growth might have an important role in clustering AChRs in the central region of muscle (Yang et al, 2000). Notably, because myoblasts fuse to developing myotubes at their growing ends, the central region of muscle is more mature than the distal ends of the muscle (Williams and Goldspink, 1971;Zhang and McLennan, 1995).…”

Section: Early Musk Expression Is Sufficient To Initiate Muscle Prepamentioning

confidence: 99%

“…This neuro-centric view of neuromuscular synapse formation, however, has been challenged by recent experiments, which showed that mammalian muscle is spatially patterned independent of innervation. In mice that lack DNA topoisomerase IIβ, motor axons fail to innervate diaphragm and limb muscles, yet AChR clusters are concentrated in the central region of these muscles (Yang et al, 2000). Subsequent studies, which examined the roles of Agrin and MuSK in nerveindependent muscle patterning, demonstrated that MuSK, but not Agrin is required to cluster AChRs in the central region of the muscle (Lin et al, 2001;Yang et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

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MuSK controls where motor axons grow and form synapses

2007

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SummaryIt had long been thought that motor axons approach muscles that are regionally unspecialized and induce postsynaptic differentiation by releasing signals that focally initiate transcriptional and post-translational responses in muscle. This neuro-centric view of synapse formation, however, has been challenged by recent experiments, which showed that AChR clusters are concentrated in the central region of muscle independent of innervation. This nerve-independent prepattern of AChR expression requires MuSK, a receptor tyrosine kinase that is critical for synapse formation. How muscle prepatterning is established and whether motor axons recognize this prepattern are not known. Here, we show that MuSK itself is prepatterned in muscle and that high, ectopic MuSK expression is sufficient to promote ectopic motor axon growth and synapse formation, indicating that the muscle prepattern is recognized by motor axons and promotes synapse formation in the central region of developing mammalian muscle. Further, we provide evidence that early expression of MuSK in developing myotubes is sufficient to re-establish muscle prepatterning independent of the MuSK promoter. Moreover, we show that ectopic MuSK expression stimulates synapse formation in the absence of Agrin and rescues the neonatal lethality of agrin mutant mice, demonstrating that MuSK, independent of Agrin, is sufficient to direct presynaptic and postsynaptic differentiation. In contrast to a neuro-centric view for synapse formation, these data demonstrate that the postsynaptic cell can play a dominant role in regulating synapse formation.

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Section: Discussionmentioning

confidence: 99%

Section: Musk Expression Is Patterned In Muscle Lacking Motor Axonsmentioning

confidence: 99%

Section: Early Musk Expression Is Sufficient To Initiate Muscle Prepamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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MuSK controls where motor axons grow and form synapses

2007

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“…High levels of topo IIα expression have been seen in aggressive proliferating tumours, whereas topo IIβ appears to be expressed ubiquitously in quiescent cells (Turley et al, 1997). Topo IIα is essential for survival of eucaryotic cells (Wang, 1996), while topo IIβ does not appear to be essential for either proliferation or survival (Yang et al, 2000;Herzog et al, 1998). Such findings may help explain the greater clinical utility of etoposide versus amsacrine.…”

Section: Resultsmentioning

confidence: 99%

Enhanced etoposide sensitivity following adenovirus-mediated human topoisomerase II α gene transfer is independent of topoisomerase II β

Zhou¹,

Zwelling

Ganapathi

et al. 2001

Br J Cancer

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The roles that the α and β isoforms of topoisomerase II (topo II) play in anticancer drug action were determined using MDA-VP etoposide-resistant human breast cancer cells and a newly constructed adenoviral vector containing the topo IIα gene (Ad-topo IIα). MDA-VP cells were more resistant to etoposide than to amsacrine and had more resistance to etoposide than did MDA-parental cells. MDA-VP cells also expressed lower topo IIα RNA and protein levels than parental cells but had comparable topo IIβ levels. After infection with Ad-topo IIα, topo IIα, RNA and protein levels increased significantly, as did the cells' sensitivity to etoposide. In contrast, topo IIβ levels remained constant with little alteration in the cells' sensitivity to amsacrine. Band-depletion immunoblotting assays indicated that topo IIα was depleted in etoposide-treated, Ad-topo IIα-transduced MDA-VP cells but not in amsacrine-treated cells. Topo IIβ was depleted in amsacrine-treated, Ad-topo IIα-MDA-VP cells, with little change in the topo IIα levels. These results suggest that topo IIα gene transfer does not alter topo IIβ expression and that enhanced sensitivity to etoposide is therefore secondary to change in topo IIα levels. These studies support the theory that etoposide preferentially targets topo IIα, while amsacrine targets topo IIβ. © 2001 Cancer Research Campaign http://www.bjcancer.com

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Topoisomerases

Sabourin

Osheroff

2002

Wiley Encyclopedia of Molecular Medicine

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DNA Topoisomerase IIβ and Neural Development

Cited by 323 publications

References 26 publications

MuSK controls where motor axons grow and form synapses

MuSK controls where motor axons grow and form synapses

Enhanced etoposide sensitivity following adenovirus-mediated human topoisomerase II α gene transfer is independent of topoisomerase II β

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