Myostatin deficiency is associated with an increase in number of total axons and motor axons innervating mouse tibialis anterior muscle

Gay, Stéphanie; Jublanc, Élodie; Bonnieu, Anne; Bacou, Francis

doi:10.1002/mus.23242

Cited by 14 publications

(13 citation statements)

References 46 publications

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“…MYO also negatively affects NMJ length and branching pattern ( ), in line with increased axonal branching in myostatin-null mice ( Gay et al, 2012 ). The lack of effect on mini amplitudes in myo overexpressing animals, despite the reduction in IIA staining, could be attributable either to a compensatory increase in the levels of other GluR subunits present at the NMJ or to GluRIIA epitope masking ( Renden and Broadie, 2003 ).…”

Section: Resultsmentioning

confidence: 92%

Myostatin-like proteins regulate synaptic function and neuronal morphology

et al. 2017

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Growth factors of the TGFβ superfamily play key roles in regulating neuronal and muscle function. Myostatin (or GDF8) and GDF11 are potent negative regulators of skeletal muscle mass. However, expression of myostatin and its cognate receptors in other tissues, including brain and peripheral nerves, suggests a potential wider biological role. Here, we show that Myoglianin (MYO), the Drosophila homolog of myostatin and GDF11, regulates not only body weight and muscle size, but also inhibits neuromuscular synapse strength and composition in a Smad2-dependent manner. Both myostatin and GDF11 affected synapse formation in isolated rat cortical neuron cultures, suggesting an effect on synaptogenesis beyond neuromuscular junctions. We also show that MYO acts in vivo to inhibit synaptic transmission between neurons in the escape response neural circuit of adult flies. Thus, these anti-myogenic proteins act as important inhibitors of synapse function and neuronal growth.

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Section: Resultsmentioning

confidence: 92%

Myostatin-like proteins regulate synaptic function and neuronal morphology

et al. 2017

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“…The increase in muscle mass is similar to that observed following post-developmental [ 31 ] inactivation of myostatin for 3–4 months [ 32 ] and slightly less than following follistatin overexpression, which results in inactivation of both myostatin and activin A [ 33 ]. Finally, in adult myostatin null mice, the two- to threefold increase in skeletal muscle mass results primarily from fiber hyperplasia and also from a 10–30 % increase in fiber hypertrophy [ 34 – 36 ]. These data suggest that in adult mice, REGN1033 fully blocks myostatin action in vivo and causes a maximal increase in muscle hypertrophy.…”

Section: Discussionmentioning

confidence: 99%

Myostatin blockade with a fully human monoclonal antibody induces muscle hypertrophy and reverses muscle atrophy in young and aged mice

et al. 2015

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BackgroundLoss of skeletal muscle mass and function in humans is associated with significant morbidity and mortality. The role of myostatin as a key negative regulator of skeletal muscle mass and function has supported the concept that inactivation of myostatin could be a useful approach for treating muscle wasting diseases.MethodsWe generated a myostatin monoclonal blocking antibody (REGN1033) and characterized its effects in vitro using surface plasmon resonance biacore and cell-based Smad2/3 signaling assays. REGN1033 was tested in mice for the ability to induce skeletal muscle hypertrophy and prevent atrophy induced by immobilization, hindlimb suspension, or dexamethasone. The effect of REGN1033 on exercise training was tested in aged mice. Messenger RNA sequencing, immunohistochemistry, and ex vivo force measurements were performed on skeletal muscle samples from REGN1033-treated mice.ResultsThe human monoclonal antibody REGN1033 is a specific and potent myostatin antagonist. Chronic treatment of mice with REGN1033 increased muscle fiber size, muscle mass, and force production. REGN1033 prevented the loss of muscle mass induced by immobilization, glucocorticoid treatment, or hindlimb unweighting and increased the gain of muscle mass during recovery from pre-existing atrophy. In aged mice, REGN1033 increased muscle mass and strength and improved physical performance during treadmill exercise.ConclusionsWe show that specific myostatin antagonism with the human antibody REGN1033 enhanced muscle mass and function in young and aged mice and had beneficial effects in models of skeletal muscle atrophy.

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“…Taken together, these studies suggest that interactions with target tissue may contribute to axonal growth. Earlier studies have observed that myostatin‐deficient mice have a larger innervation ratio, where peripheral nervous system (PNS) motor axons innervate a larger proportion of muscle fibers relative to wild‐type mice. In this study, we utilized the myostatin‐deficient mouse model to test the effect of muscle hyperplasia on total axon number, as well as structural properties of PNS sensory and motor axons.…”

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confidence: 99%

Differential effects of myostatin deficiency on motor and sensory axons

et al. 2017

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Introduction Deletion of myostatin in mice (MSTN−/−) alters structural properties of peripheral axons. However, properties like axon diameter and myelin thickness were analyzed in mixed nerves, so it is unclear if loss of myostatin affects motor, sensory or both types of axons. Methods Using the MSTN−/− mouse model, we analyzed the effects of increasing the number of muscle fibers on axon diameter, myelin thickness, and internode length in motor and sensory axons. Results Axon diameter and myelin thickness were increased in motor axons of MSTN−/− mice without affecting internode length or axon number. The number of sensory axons was increased without affecting their structural properties. Discussion These results suggest that motor and sensory axons establish structural properties by independent mechanisms. Moreover, in motor axons, instructive cues from the neuromuscular junction may play a role in co-regulating axon diameter and myelin thickness, while internode length is established independently.

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Myostatin deficiency is associated with an increase in number of total axons and motor axons innervating mouse tibialis anterior muscle

Abstract: We found that myostatin is involved either directly in the control of neuromuscular interrelationships or indirectly through its effect on muscle size.

Cited by 14 publications

References 46 publications

Myostatin-like proteins regulate synaptic function and neuronal morphology

Myostatin-like proteins regulate synaptic function and neuronal morphology

Myostatin blockade with a fully human monoclonal antibody induces muscle hypertrophy and reverses muscle atrophy in young and aged mice

Differential effects of myostatin deficiency on motor and sensory axons

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