β-Catenin gain of function in muscles impairs neuromuscular junction formation

Haitao Wu, Yisheng Lu, Arnab Barik, Anish Joseph, Makoto Mark Taketo, Wen Cheng Xiong, Lin Mei

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Neuromuscular junction (NMJ) formation requires proper interaction between motoneurons and muscle cells. β-Catenin is required in muscle cells for NMJ formation. To understand underlying mechanisms, we investigated the effect of β-catenin gain of function (GOF) on NMJ development. In HSA-β-catflox(ex3)/+ mice, which express stable β-catenin specifically in muscles, motor nerve terminals became extensively defasciculated and arborized. Ectopic muscles were observed in the diaphragm and were innervated by ectopic phrenic nerve branches. Moreover, extensive outgrowth and branching of spinal axons were evident in the GOF mice. These results indicate that increased β-catenin in muscles alters presynaptic differentiation. Postsynaptically, AChR clusters in HSA-β-catflox(ex3)/+ diaphragms were distributed in a wider region, suggesting that muscle β-catenin GOF disrupted the signal that restricts AChR clustering to the middle region of muscle fibers. Expression of stable β-catenin in motoneurons, however, had no effect on NMJ formation. These observations provide additional genetic evidence that pre- and postsynaptic development of the NMJ requires an intricate balance of β-catenin activity in muscles.

Original languageEnglish (US)
Pages (from-to)2392-2404
Number of pages13
JournalDevelopment (Cambridge)
Volume139
Issue number13
DOIs
StatePublished - Jul 1 2012

Fingerprint

Catenins
Neuromuscular Junction
Muscles
Motor Neurons
Diaphragm
Muscle Cells
Phrenic Nerve
Intercellular Junctions
Cluster Analysis
Axons

Keywords

  • β-Catenin
  • AChR
  • Axon outgrowth
  • Mouse
  • Neuromuscular junction
  • Retrograde signals

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology

Cite this

Wu, H., Lu, Y., Barik, A., Joseph, A., Taketo, M. M., Xiong, W. C., & Mei, L. (2012). β-Catenin gain of function in muscles impairs neuromuscular junction formation. Development (Cambridge), 139(13), 2392-2404. https://doi.org/10.1242/dev.080705

β-Catenin gain of function in muscles impairs neuromuscular junction formation. / Wu, Haitao; Lu, Yisheng; Barik, Arnab; Joseph, Anish; Taketo, Makoto Mark; Xiong, Wen Cheng; Mei, Lin.

In: Development (Cambridge), Vol. 139, No. 13, 01.07.2012, p. 2392-2404.

Research output: Contribution to journalArticle

Wu, H, Lu, Y, Barik, A, Joseph, A, Taketo, MM, Xiong, WC & Mei, L 2012, 'β-Catenin gain of function in muscles impairs neuromuscular junction formation', Development (Cambridge), vol. 139, no. 13, pp. 2392-2404. https://doi.org/10.1242/dev.080705
Wu H, Lu Y, Barik A, Joseph A, Taketo MM, Xiong WC et al. β-Catenin gain of function in muscles impairs neuromuscular junction formation. Development (Cambridge). 2012 Jul 1;139(13):2392-2404. https://doi.org/10.1242/dev.080705
Wu, Haitao ; Lu, Yisheng ; Barik, Arnab ; Joseph, Anish ; Taketo, Makoto Mark ; Xiong, Wen Cheng ; Mei, Lin. / β-Catenin gain of function in muscles impairs neuromuscular junction formation. In: Development (Cambridge). 2012 ; Vol. 139, No. 13. pp. 2392-2404.
@article{5fd6f58966794b32aa8acc4e50919e09,
title = "β-Catenin gain of function in muscles impairs neuromuscular junction formation",
abstract = "Neuromuscular junction (NMJ) formation requires proper interaction between motoneurons and muscle cells. β-Catenin is required in muscle cells for NMJ formation. To understand underlying mechanisms, we investigated the effect of β-catenin gain of function (GOF) on NMJ development. In HSA-β-catflox(ex3)/+ mice, which express stable β-catenin specifically in muscles, motor nerve terminals became extensively defasciculated and arborized. Ectopic muscles were observed in the diaphragm and were innervated by ectopic phrenic nerve branches. Moreover, extensive outgrowth and branching of spinal axons were evident in the GOF mice. These results indicate that increased β-catenin in muscles alters presynaptic differentiation. Postsynaptically, AChR clusters in HSA-β-catflox(ex3)/+ diaphragms were distributed in a wider region, suggesting that muscle β-catenin GOF disrupted the signal that restricts AChR clustering to the middle region of muscle fibers. Expression of stable β-catenin in motoneurons, however, had no effect on NMJ formation. These observations provide additional genetic evidence that pre- and postsynaptic development of the NMJ requires an intricate balance of β-catenin activity in muscles.",
keywords = "β-Catenin, AChR, Axon outgrowth, Mouse, Neuromuscular junction, Retrograde signals",
author = "Haitao Wu and Yisheng Lu and Arnab Barik and Anish Joseph and Taketo, {Makoto Mark} and Xiong, {Wen Cheng} and Lin Mei",
year = "2012",
month = "7",
day = "1",
doi = "10.1242/dev.080705",
language = "English (US)",
volume = "139",
pages = "2392--2404",
journal = "Development (Cambridge)",
issn = "0950-1991",
publisher = "Company of Biologists Ltd",
number = "13",

}

TY - JOUR

T1 - β-Catenin gain of function in muscles impairs neuromuscular junction formation

AU - Wu, Haitao

AU - Lu, Yisheng

AU - Barik, Arnab

AU - Joseph, Anish

AU - Taketo, Makoto Mark

AU - Xiong, Wen Cheng

AU - Mei, Lin

PY - 2012/7/1

Y1 - 2012/7/1

N2 - Neuromuscular junction (NMJ) formation requires proper interaction between motoneurons and muscle cells. β-Catenin is required in muscle cells for NMJ formation. To understand underlying mechanisms, we investigated the effect of β-catenin gain of function (GOF) on NMJ development. In HSA-β-catflox(ex3)/+ mice, which express stable β-catenin specifically in muscles, motor nerve terminals became extensively defasciculated and arborized. Ectopic muscles were observed in the diaphragm and were innervated by ectopic phrenic nerve branches. Moreover, extensive outgrowth and branching of spinal axons were evident in the GOF mice. These results indicate that increased β-catenin in muscles alters presynaptic differentiation. Postsynaptically, AChR clusters in HSA-β-catflox(ex3)/+ diaphragms were distributed in a wider region, suggesting that muscle β-catenin GOF disrupted the signal that restricts AChR clustering to the middle region of muscle fibers. Expression of stable β-catenin in motoneurons, however, had no effect on NMJ formation. These observations provide additional genetic evidence that pre- and postsynaptic development of the NMJ requires an intricate balance of β-catenin activity in muscles.

AB - Neuromuscular junction (NMJ) formation requires proper interaction between motoneurons and muscle cells. β-Catenin is required in muscle cells for NMJ formation. To understand underlying mechanisms, we investigated the effect of β-catenin gain of function (GOF) on NMJ development. In HSA-β-catflox(ex3)/+ mice, which express stable β-catenin specifically in muscles, motor nerve terminals became extensively defasciculated and arborized. Ectopic muscles were observed in the diaphragm and were innervated by ectopic phrenic nerve branches. Moreover, extensive outgrowth and branching of spinal axons were evident in the GOF mice. These results indicate that increased β-catenin in muscles alters presynaptic differentiation. Postsynaptically, AChR clusters in HSA-β-catflox(ex3)/+ diaphragms were distributed in a wider region, suggesting that muscle β-catenin GOF disrupted the signal that restricts AChR clustering to the middle region of muscle fibers. Expression of stable β-catenin in motoneurons, however, had no effect on NMJ formation. These observations provide additional genetic evidence that pre- and postsynaptic development of the NMJ requires an intricate balance of β-catenin activity in muscles.

KW - β-Catenin

KW - AChR

KW - Axon outgrowth

KW - Mouse

KW - Neuromuscular junction

KW - Retrograde signals

UR - http://www.scopus.com/inward/record.url?scp=84861991275&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84861991275&partnerID=8YFLogxK

U2 - 10.1242/dev.080705

DO - 10.1242/dev.080705

M3 - Article

C2 - 22627288

AN - SCOPUS:84861991275

VL - 139

SP - 2392

EP - 2404

JO - Development (Cambridge)

JF - Development (Cambridge)

SN - 0950-1991

IS - 13

ER -