α2-chimaerin is required for Eph receptor-class-specific spinal motor axon guidance and coordinate activation of antagonistic muscles

Tzu Jen Kao, Georgina C B Nicholl, Jamie A. Johansen, Artur Kania, Asim A. Beg

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Axonal guidance involves extrinsic molecular cues that bind growth cone receptors and signal to the cytoskeleton through divergent pathways. Some signaling intermediates are deployed downstream of molecularly distinct axon guidance receptor families, but the scope of this overlap is unclear, as is the impact of embryonic axon guidance fidelity on adult nervous system function. Here, we demonstrate that the Rho-GTPase-activating protein α2-chimaerin is specifically required for EphA and not EphB receptor signaling in mouse and chick spinal motor axons. Reflecting this specificity, the loss of α2-chimaerin function disrupts the limb trajectory of extensor-muscle-innervating motor axons the guidance of which depends on EphA signaling. These embryonic defects affect coordinated contraction of antagonistic flexor-extensor muscles in the adult, indicating that accurate embryonic motor axon guidance is critical for optimal neuromuscular function. Together, our observations provide the first functional evidence of an Eph receptor-class-specific intracellular signaling protein that is required for appropriate neuromuscular connectivity.

Original languageEnglish
Pages (from-to)2344-2357
Number of pages14
JournalJournal of Neuroscience
Volume35
Issue number6
DOIs
Publication statusPublished - 2015

Fingerprint

EphA1 Receptor
Muscles
Intracellular Signaling Peptides and Proteins
Eph Family Receptors
Growth Cones
Cytoskeleton
Nervous System
Cues
Axons
Extremities
Axon Guidance

Keywords

  • Axon guidance
  • Chimaerin
  • Motor neurons
  • Muscle contraction

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

α2-chimaerin is required for Eph receptor-class-specific spinal motor axon guidance and coordinate activation of antagonistic muscles. / Kao, Tzu Jen; Nicholl, Georgina C B; Johansen, Jamie A.; Kania, Artur; Beg, Asim A.

In: Journal of Neuroscience, Vol. 35, No. 6, 2015, p. 2344-2357.

Research output: Contribution to journalArticle

Kao, Tzu Jen ; Nicholl, Georgina C B ; Johansen, Jamie A. ; Kania, Artur ; Beg, Asim A. / α2-chimaerin is required for Eph receptor-class-specific spinal motor axon guidance and coordinate activation of antagonistic muscles. In: Journal of Neuroscience. 2015 ; Vol. 35, No. 6. pp. 2344-2357.
@article{fffb07d76d194486b2b43a69182b858d,
title = "α2-chimaerin is required for Eph receptor-class-specific spinal motor axon guidance and coordinate activation of antagonistic muscles",
abstract = "Axonal guidance involves extrinsic molecular cues that bind growth cone receptors and signal to the cytoskeleton through divergent pathways. Some signaling intermediates are deployed downstream of molecularly distinct axon guidance receptor families, but the scope of this overlap is unclear, as is the impact of embryonic axon guidance fidelity on adult nervous system function. Here, we demonstrate that the Rho-GTPase-activating protein α2-chimaerin is specifically required for EphA and not EphB receptor signaling in mouse and chick spinal motor axons. Reflecting this specificity, the loss of α2-chimaerin function disrupts the limb trajectory of extensor-muscle-innervating motor axons the guidance of which depends on EphA signaling. These embryonic defects affect coordinated contraction of antagonistic flexor-extensor muscles in the adult, indicating that accurate embryonic motor axon guidance is critical for optimal neuromuscular function. Together, our observations provide the first functional evidence of an Eph receptor-class-specific intracellular signaling protein that is required for appropriate neuromuscular connectivity.",
keywords = "Axon guidance, Chimaerin, Motor neurons, Muscle contraction",
author = "Kao, {Tzu Jen} and Nicholl, {Georgina C B} and Johansen, {Jamie A.} and Artur Kania and Beg, {Asim A.}",
year = "2015",
doi = "10.1523/JNEUROSCI.4151-14.2015",
language = "English",
volume = "35",
pages = "2344--2357",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "6",

}

TY - JOUR

T1 - α2-chimaerin is required for Eph receptor-class-specific spinal motor axon guidance and coordinate activation of antagonistic muscles

AU - Kao, Tzu Jen

AU - Nicholl, Georgina C B

AU - Johansen, Jamie A.

AU - Kania, Artur

AU - Beg, Asim A.

PY - 2015

Y1 - 2015

N2 - Axonal guidance involves extrinsic molecular cues that bind growth cone receptors and signal to the cytoskeleton through divergent pathways. Some signaling intermediates are deployed downstream of molecularly distinct axon guidance receptor families, but the scope of this overlap is unclear, as is the impact of embryonic axon guidance fidelity on adult nervous system function. Here, we demonstrate that the Rho-GTPase-activating protein α2-chimaerin is specifically required for EphA and not EphB receptor signaling in mouse and chick spinal motor axons. Reflecting this specificity, the loss of α2-chimaerin function disrupts the limb trajectory of extensor-muscle-innervating motor axons the guidance of which depends on EphA signaling. These embryonic defects affect coordinated contraction of antagonistic flexor-extensor muscles in the adult, indicating that accurate embryonic motor axon guidance is critical for optimal neuromuscular function. Together, our observations provide the first functional evidence of an Eph receptor-class-specific intracellular signaling protein that is required for appropriate neuromuscular connectivity.

AB - Axonal guidance involves extrinsic molecular cues that bind growth cone receptors and signal to the cytoskeleton through divergent pathways. Some signaling intermediates are deployed downstream of molecularly distinct axon guidance receptor families, but the scope of this overlap is unclear, as is the impact of embryonic axon guidance fidelity on adult nervous system function. Here, we demonstrate that the Rho-GTPase-activating protein α2-chimaerin is specifically required for EphA and not EphB receptor signaling in mouse and chick spinal motor axons. Reflecting this specificity, the loss of α2-chimaerin function disrupts the limb trajectory of extensor-muscle-innervating motor axons the guidance of which depends on EphA signaling. These embryonic defects affect coordinated contraction of antagonistic flexor-extensor muscles in the adult, indicating that accurate embryonic motor axon guidance is critical for optimal neuromuscular function. Together, our observations provide the first functional evidence of an Eph receptor-class-specific intracellular signaling protein that is required for appropriate neuromuscular connectivity.

KW - Axon guidance

KW - Chimaerin

KW - Motor neurons

KW - Muscle contraction

UR - http://www.scopus.com/inward/record.url?scp=84922575647&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84922575647&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.4151-14.2015

DO - 10.1523/JNEUROSCI.4151-14.2015

M3 - Article

VL - 35

SP - 2344

EP - 2357

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 6

ER -