Temporal transcription factors determine circuit membership by altering motor neuron-to-muscle synaptic partnerships

Abstract

Previously, using the Drosophila motor system as a model, we found the classic temporal transcription factor, Hunchback acts in NB7-1 neuronal stem cells as a molecular switch to control which circuits are populated by NB7-1 neuronal progeny (Meng et al., 2019). Here, we manipulate cardinal transcription factors, Nkx6 and Hb9, which are candidate effectors of Hunchback and which alter axon pathfinding in embryos. Yet manipulation of these cardinal transcription factors does not permanently alter neuromuscular synaptic partnerships. This demonstrates that compensation can correct early defects. We perform additional temporal transcription factor manipulations, precociously expressing Pdm and Castor in NB7-1 and prolonging expression of Hunchback in NB3-1. In every case, we find permanent alterations in neuromuscular synaptic partnerships. These data support the idea that temporal transcription factors are uniquely potent determinants of circuit membership, which do not trigger compensatory programs because they act to establish the expected pattern of wiring for the motor system.