Myostatin-like proteins regulate synaptic function and neuronal morphology

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


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.

MeSH terms

  • Animals
  • Body Weight
  • Cell Shape*
  • Down-Regulation / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / metabolism*
  • Gene Silencing
  • Glycogen Synthase Kinase 3 / metabolism
  • Growth Differentiation Factors / metabolism
  • Humans
  • Larva / metabolism
  • Muscle Cells / metabolism
  • Myostatin / metabolism*
  • Neuroglia / metabolism
  • Neuromuscular Junction / metabolism
  • Neurons / cytology*
  • Neurons / metabolism*
  • Rats
  • Signal Transduction
  • Synapses / metabolism*
  • Synaptic Transmission
  • Transforming Growth Factor beta / metabolism*


  • Drosophila Proteins
  • Gdf11 protein, rat
  • Growth Differentiation Factors
  • MSTN protein, human
  • Myostatin
  • Transforming Growth Factor beta
  • myo protein, Drosophila
  • Sgg protein, Drosophila
  • Glycogen Synthase Kinase 3