Genetic Evidence for a Contribution of EphA:EphrinA Reverse Signaling to Motor Axon Guidance

Dudanova, Irina; Kao, Tzu-Jen; Herrmann, Julia; Zheng, Binhai; Kania, Artur; Klein, Rüdiger

doi:10.1523/jneurosci.5707-11.2012

Cited by 40 publications

(28 citation statements)

References 33 publications

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“…These include reverse signaling from EphA4 to ephrin-A5 in LMC axons, attraction to limbexpressed GDNF via c-Ret, and repulsion from Semaphorin 3A (Huber et al, 2005;Kramer et al, 2006;Dudanova et al, 2010;Bonanomi et al, 2012;Dudanova et al, 2012). Might ␣2-chimaerin function in these processes contribute to the in vivo guidance phenotypes observed in ␣2 gt/gt mutants?…”

Section: Discussionmentioning

confidence: 99%

α2-Chimaerin Is Required for Eph Receptor-Class-Specific Spinal Motor Axon Guidance and Coordinate Activation of Antagonistic Muscles

et al. 2015

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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 ␣2-chimaerin is specifically required for EphA and not EphB receptor signaling in mouse and chick spinal motor axons. Reflecting this specificity, the loss of ␣2-chimaerin function disrupts the limb trajectory of extensor-muscleinnervating 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.

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Section: Discussionmentioning

confidence: 99%

α2-Chimaerin Is Required for Eph Receptor-Class-Specific Spinal Motor Axon Guidance and Coordinate Activation of Antagonistic Muscles

et al. 2015

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“…Ephrin forward and reverse signaling has been characterized as guiding the axonal projections of limb-innervating motor neurons (32,38,39), and α2-chimaerin is known to act downstream of ephrin forward signaling in several neuronal types (12)(13)(14)(15), including limb motor neurons (29). We expand on these findings to define the involvement of EphA4-mediated ephrin forward and reverse signaling in abducens nerve development and in a human developmental disorder.…”

Section: Neuronal and Mesenchymal Epha4 Conditional Knockouts Reveal mentioning

confidence: 91%

Mutant α2-chimaerin signals via bidirectional ephrin pathways in Duane retraction syndrome

Nugent¹,

Park²,

Wei³

et al. 2017

Journal of Clinical Investigation

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Duane retraction syndrome (DRS) is the most common form of congenital paralytic strabismus in humans and can result from α2-chimaerin (CHN1) missense mutations. We report a knockin α2-chimaerin mouse (Chn1 abducens neurons use bidirectional ephrin signaling via mutant α2-chimaerin to direct growth, while cervical spinal neurons use only ephrin forward signaling, and trochlear neurons do not use ephrin signaling. These findings reveal a role for ephrin bidirectional signaling upstream of mutant α2-chimaerin in DRS, which may contribute to the selective vulnerability of abducens motor neurons in this disorder.

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“…Hence, forward and reverse signalling can occur in parallel. Reverse signalling from limb-derived EphA4 to axonal ephrin A proteins results in attraction of LMC L axons towards the dorsal limb (Kao and Kania, 2011;Dudanova et al, 2012). In LMC M axons, EphA4 signalling is attenuated by cis interaction with ephrin A proteins, providing an explanation for the failure of these axons to be repelled by the ephrin A-positive ventral limb.…”

Section: Decision Making At Intermediate Targets -Binary Choicesmentioning

confidence: 99%

Eph/ephrin signalling during development

2012

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Eph receptors and their membrane-tethered ligands have important functions in development. Trans interactions of Eph receptors with ephrins at cell-cell interfaces promote a variety of cellular responses, including repulsion, attraction and migration. Eph-ephrin signalling can be bi-directional and controls actin cytoskeleton dynamics, thereby leading to changes in cellular shape. This article provides an overview of the general structures and signalling mechanisms, and of typical developmental functions along with cell biological principles.

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Genetic Evidence for a Contribution of EphA:EphrinA Reverse Signaling to Motor Axon Guidance

Cited by 40 publications

References 33 publications

α2-Chimaerin Is Required for Eph Receptor-Class-Specific Spinal Motor Axon Guidance and Coordinate Activation of Antagonistic Muscles

α2-Chimaerin Is Required for Eph Receptor-Class-Specific Spinal Motor Axon Guidance and Coordinate Activation of Antagonistic Muscles

Mutant α2-chimaerin signals via bidirectional ephrin pathways in Duane retraction syndrome

Eph/ephrin signalling during development

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