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

Abstract

<jats:title>Abstract</jats:title><jats:p>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.</jats:p>

Structural and Functional Synaptic Plasticity Induced by Convergent Synapse Loss in theDrosophilaNeuromuscular Circuit

“…All recordings were performed as previously described (Meng et al, 2020). Third instar larvae were dissected in modified HL3 saline (70 mM NaCl, 5 mM KCl, 10 mM MgCl2, 10 mM NaHCO3, 5 mM Trehelose, 115 mM Sucrose, 5 mM HEPES) with 0.3 mM calcium.…”

Structural and functional synaptic plasticity induced by convergent synapse loss requires co-innervation in the Drosophila neuromuscular circuit

“…Laser 161 intensity, pinhole and gain were adjusted to increase the signal but avoid overexposure. All All recordings were performed as previously described (Meng et al, 2020). Third instar larvae 178 were dissected in modified HL3 saline (70 mM NaCl, 5 mM KCl, 10 mM MgCl2, 10 mM 179 NaHCO3, 5 mM Trehelose, 115 mM Sucrose, 5 mM HEPES) with 0.3 mM calcium.…”

Sequential addition of neuronal stem cell temporal cohorts generates a feed-forward circuit in the Drosophila larval nerve cord

“…These data linked temporal cohorts to differential circuit function. More recently, in other lineages (i.e., NB1-2, NB2-1, NB3-1, NB4-1, NB5-2, NB7-1, NB 7-4), neurons within temporal cohorts were shown to share similarities in their synaptic partnerships (Meng et al, 2019)(Meng et al, 2020)(Mark et al, 2021). Furthermore, the number of neurons in lineage that are segregated into a given temporal cohorts can be altered by manipulating temporal factor expression in neuronal stem cells (Meng et al, 2019)(Meng et al, 2020).…”

“…More recently, in other lineages (i.e., NB1-2, NB2-1, NB3-1, NB4-1, NB5-2, NB7-1, NB 7-4), neurons within temporal cohorts were shown to share similarities in their synaptic partnerships (Meng et al, 2019)(Meng et al, 2020)(Mark et al, 2021). Furthermore, the number of neurons in lineage that are segregated into a given temporal cohorts can be altered by manipulating temporal factor expression in neuronal stem cells (Meng et al, 2019)(Meng et al, 2020). Thus, temporal cohorts are developmental units that likely to be specified early during neurogenesis in a lineage intrinsic manner by the molecular programs known to generate neural diversity.…”

“…For many neuronal features, such as morphology, gene expression, and neurotransmitter phenotype, there can be sharp changes in lineage progression. For example, a neuroblast can abruptly change from producing motor neurons to interneurons (Meng et al, 2020) or from producing Eve(+) to Eve(−) neurons (Pearson & Doe, 2003). The idea that temporal cohorts have distinct circuit-level function suggests that there are also sharp changes in the patterns of synaptic partnerships formed by neurons in a lineage, and that these sharp changes are correlated with temporal cohort borders.…”