Axonal filopodial asymmetry induced by synaptic target

Pan Li, G. Chen, Chi Wai Lee, Raghavan Madhavan, H. Benjamin Peng

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2480-2490
Number of pages11
JournalMolecular Biology of the Cell
Volume22
Issue number14
DOIs
StatePublished - Jul 15 2011
Externally publishedYes

Fingerprint

Fibroblast Growth Factor 2
Fibroblast Growth Factor 1
Fibroblast Growth Factor Receptors
Muscles
Pseudopodia
Neurons
Neuromuscular Junction
Axons
Cholinergic Receptors
Neurites
Coculture Techniques
Xenopus
Immunoblotting
Vertebrates

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Axonal filopodial asymmetry induced by synaptic target. / Li, Pan; Chen, G.; Lee, Chi Wai; Madhavan, Raghavan; Peng, H. Benjamin.

In: Molecular Biology of the Cell, Vol. 22, No. 14, 15.07.2011, p. 2480-2490.

Research output: Contribution to journalArticle

Li, P, Chen, G, Lee, CW, Madhavan, R & Peng, HB 2011, 'Axonal filopodial asymmetry induced by synaptic target', Molecular Biology of the Cell, vol. 22, no. 14, pp. 2480-2490. https://doi.org/10.1091/mbc.E11-03-0198
Li, Pan ; Chen, G. ; Lee, Chi Wai ; Madhavan, Raghavan ; Peng, H. Benjamin. / Axonal filopodial asymmetry induced by synaptic target. In: Molecular Biology of the Cell. 2011 ; Vol. 22, No. 14. pp. 2480-2490.
@article{2a1c62843ea143b9b69cab4961ccd2d2,
title = "Axonal filopodial asymmetry induced by synaptic target",
abstract = "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.",
author = "Pan Li and G. Chen and Lee, {Chi Wai} and Raghavan Madhavan and Peng, {H. Benjamin}",
year = "2011",
month = "7",
day = "15",
doi = "10.1091/mbc.E11-03-0198",
language = "English (US)",
volume = "22",
pages = "2480--2490",
journal = "Molecular Biology of the Cell",
issn = "1059-1524",
publisher = "American Society for Cell Biology",
number = "14",

}

TY - JOUR

T1 - Axonal filopodial asymmetry induced by synaptic target

AU - Li, Pan

AU - Chen, G.

AU - Lee, Chi Wai

AU - Madhavan, Raghavan

AU - Peng, H. Benjamin

PY - 2011/7/15

Y1 - 2011/7/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=79960290138&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960290138&partnerID=8YFLogxK

U2 - 10.1091/mbc.E11-03-0198

DO - 10.1091/mbc.E11-03-0198

M3 - Article

VL - 22

SP - 2480

EP - 2490

JO - Molecular Biology of the Cell

JF - Molecular Biology of the Cell

SN - 1059-1524

IS - 14

ER -