Transsynaptic BMP Signaling Regulates Fine-Scale Topography between Adjacent Sensory Neurons

eNeuro. 2024 Aug 28;11(8):ENEURO.0322-24.2024. doi: 10.1523/ENEURO.0322-24.2024. Print 2024 Aug.

Abstract

Sensory axons projecting to the central nervous system are organized into topographic maps that represent the locations of sensory stimuli. In some sensory systems, even adjacent sensory axons are arranged topographically, forming "fine-scale" topographic maps. Although several broad molecular gradients are known to instruct coarse topography, we know little about the molecular signaling that regulates fine-scale topography at the level of two adjacent axons. Here, we provide evidence that transsynaptic bone morphogenetic protein (BMP) signaling mediates local interneuronal communication to regulate fine-scale topography in the nociceptive system of Drosophila larvae. We first show that the topographic separation of the axon terminals of adjacent nociceptors requires their common postsynaptic target, the A08n neurons. This phenotype is recapitulated by knockdown of the BMP ligand, Decapentaplegic (Dpp), in these neurons. In addition, removing the Type 2 BMP receptors or their effector (Mad transcription factor) in single nociceptors impairs the fine-scale topography, suggesting the contribution of BMP signaling originated from A08n. This signaling is likely mediated by phospho-Mad in the presynaptic terminals of nociceptors to ensure local interneuronal communication. Finally, reducing Dpp levels in A08n reduces the nociceptor-A08n synaptic contacts. Our data support that transsynaptic BMP signaling establishes the fine-scale topography by facilitating the formation of topographically correct synapses. Local BMP signaling for synapse formation may be a developmental strategy that independently regulates neighboring axon terminals for fine-scale topography.

Keywords: BMP signaling; Drosophila; axon; sensory; topography.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Bone Morphogenetic Proteins* / metabolism
  • DNA-Binding Proteins
  • Drosophila
  • Drosophila Proteins* / metabolism
  • Larva
  • Nociceptors / metabolism
  • Nociceptors / physiology
  • Presynaptic Terminals / metabolism
  • Presynaptic Terminals / physiology
  • Sensory Receptor Cells* / metabolism
  • Sensory Receptor Cells* / physiology
  • Signal Transduction* / physiology
  • Synapses / metabolism
  • Synapses / physiology
  • Transcription Factors

Substances

  • Drosophila Proteins
  • Bone Morphogenetic Proteins
  • dpp protein, Drosophila
  • MAD protein, Drosophila
  • DNA-Binding Proteins
  • Transcription Factors