Temporal Cohorts of Lineage-Related Neurons Perform Analogous Functions in Distinct Sensorimotor Circuits

Curr Biol. 2017 May 22;27(10):1521-1528.e4. doi: 10.1016/j.cub.2017.04.024. Epub 2017 May 11.


Neuronal stem cell lineages are the fundamental developmental units of the brain, and neuronal circuits are the fundamental functional units of the brain. Determining lineage-circuitry relationships is essential for deciphering the developmental logic of circuit assembly. While the spatial distribution of lineage-related neurons has been investigated in a few brain regions [1-9], an important, but unaddressed question is whether temporal information that diversifies neuronal progeny within a single lineage also impacts circuit assembly. Circuits in the sensorimotor system (e.g., spinal cord) are thought to be assembled sequentially [10-14], making this an ideal brain region for investigating the circuit-level impact of temporal patterning within a lineage. Here, we use intersectional genetics, optogenetics, high-throughput behavioral analysis, single-neuron labeling, connectomics, and calcium imaging to determine how a set of bona fide lineage-related interneurons contribute to sensorimotor circuitry in the Drosophila larva. We show that Even-skipped lateral interneurons (ELs) are sensory processing interneurons. Late-born ELs contribute to a proprioceptive body posture circuit, whereas early-born ELs contribute to a mechanosensitive escape circuit. These data support a model in which a single neuronal stem cell can produce a large number of interneurons with similar functional capacity that are distributed into different circuits based on birth timing. In summary, these data establish a link between temporal specification of neuronal identity and circuit assembly at the single-cell level.

Keywords: Eve lateral; NB3-3; cell lineage; chordotonal; escape; neural circuit; neuroblast; proprioception; temporal identity; transmission electronic microscopy.

MeSH terms

  • Animals
  • Behavior, Animal
  • Cell Lineage*
  • Drosophila melanogaster / cytology*
  • Drosophila melanogaster / growth & development*
  • Drosophila melanogaster / metabolism
  • Embryo, Nonmammalian / cytology
  • Larva / cytology
  • Larva / metabolism
  • Mechanotransduction, Cellular
  • Neurons / cytology*
  • Neurons / metabolism
  • Sensorimotor Cortex / cytology
  • Sensorimotor Cortex / metabolism*