How prolonged expression of Hunchback, a temporal transcription factor, re-wires locomotor circuits

Abstract

How circuits assemble starting from stem cells is a fundamental question in developmental neurobiology. We test the hypothesis that, in neuronal stem cells, temporal transcription factors predictably control neuronal terminal features and circuit assembly. Using the Drosophila motor system, we manipulate expression of the classic temporal transcription factor Hunchback (Hb) specifically in the NB7-1 stem cell, which produces U motor neurons (MNs), and then we monitor dendrite morphology and neuromuscular synaptic partnerships. We find that prolonged expression of Hb leads to transient specification of U MN identity, and that embryonic molecular markers do not accurately predict U MN terminal features. Nonetheless, our data show Hb acts as a potent regulator of neuromuscular wiring decisions. These data introduce important refinements to current models, show that molecular information acts early in neurogenesis as a switch to control motor circuit wiring, and provide novel insight into the relationship between stem cell and circuit.

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

“…These data suggest the existence of compensation that can repair early developmental defects. These findings are in contrast to our previous work showing that the temporal transcription factor, Hunchback acting in NB7-1 can permanently alter motor neuron-to-muscle synaptic partnerships (Meng et al, 2019). This contrast highlights Hunchback's potency to regulate circuit membership.…”

“…Temporal transcription factors also control neurotransmitter expression in embryonic neurons (Stratmann and Thor, 2017;Isshiki et al, 2001, Allan andThor, 2015). In Drosophila mushroom body, central complex, and nerve cord, temporal transcription factors control axon and dendrite targeting and neuron morphology (Pearson and Doe, 2003;Seroka and Doe 2019;Meng et al, 2019, Sullivan et al, 2019Rossi et al, 2017;Doe et al, 2017). These data demonstrate temporal transcription factors regulate the early decisions a neuron makes towards circuit membership.…”

“…Although Eyeless controls morphology, it is unknown how Eyeless impacts synaptic partner selection and function of altered neurons. Another recent study in Drosophila nerve cord showed that prolonged expression of the temporal transcription factor, Hunchback, in one neuronal stem cell, n euro b last (NB) 7-1 impacts functional synaptic connections made by NB7-1 progeny (Meng, et al 2019). Specifically, expression of Hunchback increases the total number of Even-skipped expressing (herein: Eve(+)) motor neurons made by NB7-1 without significantly extending the total number of neurons produced in the NB7-1 lineage.…”

“…Specifically, expression of Hunchback increases the total number of Even-skipped expressing (herein: Eve(+)) motor neurons made by NB7-1 without significantly extending the total number of neurons produced in the NB7-1 lineage. In wild type larvae, Eve(+) motor neurons exit the CNS, travel to the dorsal muscle field and make functional synaptic connections on a subset of dorsal muscles (Meng et al, 2019), and the ectopic Eve(+) motor neurons generated by prolonged expression of Hunchback also project to and form synaptic connections with muscles in the dorsal muscle field (Meng et al, 2019). Therefore, Hunchback expression in neuroblast, NB7-1 determines how many of the lineage's neuronal progeny populate the dorsal muscle circuit.…”

“…

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.

…”