Early nerve–muscle interaction that leads to neuromuscular junction formation is mediated by axonal filopodia that are oriented preferentially toward the muscle as a result of target-derived basic fibroblast growth factor

Amaya E

Arikkath J

Cheng Chen

Chi-Wai Lee

Dai Z

Dailey ME

Eswarakumar VP

Feng Z

Fertuck HC

Fitzsimonds RM

Fox MA

Gallagher JT

Gallo G

Gerrow K

Gonzalez AM

H. Benjamin Peng

Heiman MG

Kalil K

Ketschek A

Kim N

Kummer TT

Kusakabe M

Lee CW

Madhavan R

Nishimune H

Pan P. Li

Peng HB

Raghavan Madhavan

Ritzenthaler S

Sanes JR

Sekino Y

Szebenyi G

Terauchi A

Thomas D. Pollard

Uhm CS

Umemori H

Yoshihara Y

Zhang B

Ziv NE

PubMed

During vertebrate neuromuscular junction (NMJ) assembly, motor axons and their muscle targets exchange short-range signals that regulate the subsequent steps of presynaptic and postsynaptic specialization. We report here that this interaction is in part mediated by axonal filopodia extended preferentially by cultured Xenopus spinal neurons toward their muscle targets. Immunoblotting and labeling experiments showed that basic fibroblast growth factor (bFGF) was expressed by muscle and associated with the cell surface, and treatment of cultured spinal neurons with recombinant bFGF nearly doubled the normal density of filopodia in neurites. This effect of bFGF was abolished by SU5402, a selective inhibitor of FGF-receptor 1 (FGFR1), and forced expression of wild-type or dominant-negative FGFR1 in neurons enhanced or suppressed the assembly of filopodia, respectively. Significantly, in nerve-muscle cocultures, knocking down bFGF in muscle decreased both the asymmetric extension of filopodia by axons toward muscle and the assembly of NMJs. In addition, neurons expressing dominant-negative FGFR1 less effectively triggered the aggregation of muscle acetylcholine receptors at innervation sites than did control neurons. These results suggest that bFGF activation of neuronal FGFR1 generates filopodial processes in neurons that promote nerve-muscle interaction and facilitate NMJ establishment

Li, Pan P.

Chen, Cheng

Lee, Chi-Wai

Madhavan, Raghavan

Peng, H. Benjamin

Hong Kong University of Science and Technology Institutional Repository

Molecular Biology of the Cell

Axonal filopodial asymmetry induced by synaptic target

 During vertebrate neuromuscular junction (NMJ) assembly, motor axons and their muscle targets exchange short-range signals that regulate the subsequent steps of presynaptic and postsynaptic specialization. We report here that this interaction is in part mediated by axonal filopodia extended preferentially by cultured Xenopus spinal neurons toward their muscle targets. Immunoblotting and labeling experiments showed that basic fibroblast growth factor (bFGF) was expressed by muscle and associated with the cell surface, and treatment of cultured spinal neurons with recombinant bFGF nearly doubled the normal density of filopodia in neurites. This effect of bFGF was abolished by SU5402, a selective inhibitor of FGF-receptor 1 (FGFR1), and forced expression of wild-type or dominant-negative FGFR1 in neurons enhanced or suppressed the assembly of filopodia, respectively. Significantly, in nerve–muscle cocultures, knocking down bFGF in muscle decreased both the asymmetric extension of filopodia by axons toward muscle and the assembly of NMJs. In addition, neurons expressing dominant-negative FGFR1 less effectively triggered the aggregation of muscle acetylcholine receptors at innervation sites than did control neurons. These results suggest that bFGF activation of neuronal FGFR1 generates filopodial processes in neurons that promote nerve–muscle interaction and facilitate NMJ establishment. </jats:p

Crossref

During vertebrate neuromuscular junction (NMJ) assembly, motor axons and their muscle targets exchange short-range signals that regulate the subsequent steps of presynaptic and postsynaptic specialization. We report here that this interaction is in part mediated by axonal filopodia extended preferentially by cultured Xenopus spinal neurons toward their muscle targets. Immunoblotting and labeling experiments showed that basic fibroblast growth factor (bFGF) was expressed by muscle and associated with the cell surface, and treatment of cultured spinal neurons with recombinant bFGF nearly doubled the normal density of filopodia in neurites. This effect of bFGF was abolished by SU5402, a selective inhibitor of FGF-receptor 1 (FGFR1), and forced expression of wild-type or dominant-negative FGFR1 in neurons enhanced or suppressed the assembly of filopodia, respectively. Significantly, in nerve-muscle cocultures, knocking down bFGF in muscle decreased both the asymmetric extension of filopodia by axons toward muscle and the assembly of NMJs. In addition, neurons expressing dominant-negative FGFR1 less effectively triggered the aggregation of muscle acetylcholine receptors at innervation sites than did control neurons. These results suggest that bFGF activation of neuronal FGFR1 generates filopodial processes in neurons that promote nerve-muscle interaction and facilitate NMJ establishment.published_or_final_versio

Li, PP

Chen, C

Lee, CW

Madhavan, R

Peng, HB

HKU Scholars Hub

http://repository.ust.hk/ir/bitstream/1783.1-7280/1/Axonal.pdf

Axonal filopodial asymmetry induced by synaptic target

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Hong Kong University of Science and Technology Institutional Repository

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HKU Scholars Hub