Ephexin1 is required for Eph-Mediated limb trajectory of spinal motor axons

Chih Ju Chang, Ming Yuan Chang, Szu Yi Chou, Chi Chen Huang, Jian Ying Chuang, Tsung I. Hsu, Hsing Fang Chang, Yi Hsin Wu, Chung Che Wu, Daniel Morales, Artur Kania, Tzu Jen Kao

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The precise assembly of a functional nervous system relies on the guided migration of axonal growth cones, which is made possible by signals transmitted to the cytoskeleton by cell surface-expressed guidance receptors. We investigated the function of ephexin1, a Rho guanine nucleotide exchange factor, as an essential growth-cone guidance intermediary in the context of spinal lateral motor column (LMC) motor axon trajectory selection in the limb mesenchyme. Using in situm RNA detection, we first show that ephexin1 is expressed in LMC neurons of chick and mouse embryos at the time of spinal motor axon extension into the limb. Ephexin1 loss of function and gain of function using in ovo electroporation in chick LMC neurons, of either sex, perturbed LMC axontrajectory selection, demonstratingan essential role of ephexin1 in motoraxonguidance. Inaddition, ephexin1loss inmice of eithersexled to LMC axontrajectory selection errors.Wealsoshowthatephexin1knockdownattenuates the growth preference of LMC neurites against ephrins in vitro and Eph receptor-mediated retargeting of LMC axons in vivo, suggesting that ephexin1 is required in Eph-mediated LMC motor axon guidance. Finally, boThephexin1 knockdown and ectopic expression of nonphosphorylatable ephexin1 mutant attenuated the retargeting of LMC axons caused by Src overexpression, implicating ephexin1 as an Src target in Eph signal relay in this context. In summary, our findings demonstrate that ephexin1 is essential for motor axon guidance and suggest an important role in relaying ephrin:Eph signals that mediate motor axon trajectory selection.

Original languageEnglish
Pages (from-to)2043-2056
Number of pages14
JournalJournal of Neuroscience
Volume38
Issue number8
DOIs
Publication statusPublished - Feb 21 2018

Fingerprint

Axons
Extremities
Ephrins
Growth Cones
Motor Neurons
EphA1 Receptor
Rho Guanine Nucleotide Exchange Factors
Electroporation
Mesoderm
Neurites
Chick Embryo
Cytoskeleton
Nervous System
RNA
Growth
Axon Guidance

Keywords

  • Axon guidance
  • Motor neuron
  • Spinal cord

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Ephexin1 is required for Eph-Mediated limb trajectory of spinal motor axons. / Chang, Chih Ju; Chang, Ming Yuan; Chou, Szu Yi; Huang, Chi Chen; Chuang, Jian Ying; Hsu, Tsung I.; Chang, Hsing Fang; Wu, Yi Hsin; Wu, Chung Che; Morales, Daniel; Kania, Artur; Kao, Tzu Jen.

In: Journal of Neuroscience, Vol. 38, No. 8, 21.02.2018, p. 2043-2056.

Research output: Contribution to journalArticle

Chang, Chih Ju ; Chang, Ming Yuan ; Chou, Szu Yi ; Huang, Chi Chen ; Chuang, Jian Ying ; Hsu, Tsung I. ; Chang, Hsing Fang ; Wu, Yi Hsin ; Wu, Chung Che ; Morales, Daniel ; Kania, Artur ; Kao, Tzu Jen. / Ephexin1 is required for Eph-Mediated limb trajectory of spinal motor axons. In: Journal of Neuroscience. 2018 ; Vol. 38, No. 8. pp. 2043-2056.
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AU - Chang, Chih Ju

AU - Chang, Ming Yuan

AU - Chou, Szu Yi

AU - Huang, Chi Chen

AU - Chuang, Jian Ying

AU - Hsu, Tsung I.

AU - Chang, Hsing Fang

AU - Wu, Yi Hsin

AU - Wu, Chung Che

AU - Morales, Daniel

AU - Kania, Artur

AU - Kao, Tzu Jen

PY - 2018/2/21

Y1 - 2018/2/21

N2 - The precise assembly of a functional nervous system relies on the guided migration of axonal growth cones, which is made possible by signals transmitted to the cytoskeleton by cell surface-expressed guidance receptors. We investigated the function of ephexin1, a Rho guanine nucleotide exchange factor, as an essential growth-cone guidance intermediary in the context of spinal lateral motor column (LMC) motor axon trajectory selection in the limb mesenchyme. Using in situm RNA detection, we first show that ephexin1 is expressed in LMC neurons of chick and mouse embryos at the time of spinal motor axon extension into the limb. Ephexin1 loss of function and gain of function using in ovo electroporation in chick LMC neurons, of either sex, perturbed LMC axontrajectory selection, demonstratingan essential role of ephexin1 in motoraxonguidance. Inaddition, ephexin1loss inmice of eithersexled to LMC axontrajectory selection errors.Wealsoshowthatephexin1knockdownattenuates the growth preference of LMC neurites against ephrins in vitro and Eph receptor-mediated retargeting of LMC axons in vivo, suggesting that ephexin1 is required in Eph-mediated LMC motor axon guidance. Finally, boThephexin1 knockdown and ectopic expression of nonphosphorylatable ephexin1 mutant attenuated the retargeting of LMC axons caused by Src overexpression, implicating ephexin1 as an Src target in Eph signal relay in this context. In summary, our findings demonstrate that ephexin1 is essential for motor axon guidance and suggest an important role in relaying ephrin:Eph signals that mediate motor axon trajectory selection.

AB - The precise assembly of a functional nervous system relies on the guided migration of axonal growth cones, which is made possible by signals transmitted to the cytoskeleton by cell surface-expressed guidance receptors. We investigated the function of ephexin1, a Rho guanine nucleotide exchange factor, as an essential growth-cone guidance intermediary in the context of spinal lateral motor column (LMC) motor axon trajectory selection in the limb mesenchyme. Using in situm RNA detection, we first show that ephexin1 is expressed in LMC neurons of chick and mouse embryos at the time of spinal motor axon extension into the limb. Ephexin1 loss of function and gain of function using in ovo electroporation in chick LMC neurons, of either sex, perturbed LMC axontrajectory selection, demonstratingan essential role of ephexin1 in motoraxonguidance. Inaddition, ephexin1loss inmice of eithersexled to LMC axontrajectory selection errors.Wealsoshowthatephexin1knockdownattenuates the growth preference of LMC neurites against ephrins in vitro and Eph receptor-mediated retargeting of LMC axons in vivo, suggesting that ephexin1 is required in Eph-mediated LMC motor axon guidance. Finally, boThephexin1 knockdown and ectopic expression of nonphosphorylatable ephexin1 mutant attenuated the retargeting of LMC axons caused by Src overexpression, implicating ephexin1 as an Src target in Eph signal relay in this context. In summary, our findings demonstrate that ephexin1 is essential for motor axon guidance and suggest an important role in relaying ephrin:Eph signals that mediate motor axon trajectory selection.

KW - Axon guidance

KW - Motor neuron

KW - Spinal cord

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