Tao Negatively Regulates BMP Signaling During Neuromuscular Junction Development in Drosophila

Dev Neurobiol. 2019 Apr;79(4):335-349. doi: 10.1002/dneu.22681. Epub 2019 May 11.

Abstract

The coordinated growth and development of synapses is critical for all aspects of neural circuit function and mutations that disrupt these processes can result in various neurological defects. Several anterograde and retrograde signaling pathways, including the canonical Bone Morphogenic Protein (BMP) pathway, regulate synaptic development in vertebrates and invertebrates. At the Drosophila larval neuromuscular junction (NMJ), the retrograde BMP pathway is a part of the machinery that controls NMJ expansion concurrent with larval growth. We sought to determine whether the conserved Hippo pathway, critical for proportional growth in other tissues, also functions in NMJ development. We found that neuronal loss of the serine-threonine protein kinase Tao, a regulator of the Hippo signaling pathway, results in supernumerary boutons which contain a normal density of active zones. Tao is also required for proper synaptic function, as reduction of Tao results in NMJs with decreased evoked excitatory junctional potentials. Surprisingly, Tao function in NMJ growth is independent of the Hippo pathway. Instead, our experiments suggest that Tao negatively regulates BMP signaling as reduction of Tao leads to an increase in pMad levels in motor neuron nuclei and an increase in BMP target gene expression. Taken together, these results support a role for Tao as a novel inhibitor of BMP signaling in motor neurons during synaptic development and function.

Keywords: BMP signaling; Hippo signaling; NMJ development; Tao.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Bone Morphogenetic Proteins / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster
  • Neuromuscular Junction / enzymology*
  • Neuromuscular Junction / growth & development*
  • Neuronal Outgrowth / physiology
  • Presynaptic Terminals / enzymology
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Signal Transduction
  • Synaptic Transmission / physiology

Substances

  • Bone Morphogenetic Proteins
  • Drosophila Proteins
  • Protein-Serine-Threonine Kinases
  • Tao protein, Drosophila