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Development. 2017 Jul 1;144(13):2445-2455. doi: 10.1242/dev.152975. Epub 2017 May 22.

Myostatin-like proteins regulate synaptic function and neuronal morphology.

Author information

1
Institute of Healthy Ageing, and GEE, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK.
2
Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Str. 9b, Cologne D-50931, Germany.
3
Institute of Structural and Molecular Biology, University College London, Darwin Building Gower Street, London WC1E 6BT, UK.
4
MRC Toxicology Unit, Hodgkin Building, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK.
5
MRC Clinical Sciences Centre, Du Cane Road, London W12 0NN, UK.
6
Institute of Clinical Sciences, Imperial College London, ICTEM Building, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK.
7
Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.
8
Institute of Healthy Ageing, and GEE, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK partridge@age.mpg.de.

Abstract

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.

KEYWORDS:

Drosophila; GDF11; Muscle size; Myoglianin; Myostatin; Synapse

PMID:
28533206
PMCID:
PMC5536874
DOI:
10.1242/dev.152975
[Indexed for MEDLINE]
Free PMC Article

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