Hunchback activates Bicoid in Pair1 neurons to regulate synapse number and locomotor circuit function.

Neural circuit function underlies cognition, sensation, and behavior. Proper circuit assembly depends on the identity of the neurons in the circuit (gene expression, morphology, synapse targeting, and biophysical properties). Neuronal identity is established by spatial and temporal patterning mechanisms, but little is known about how these mechanisms drive circuit formation in postmitotic neurons. Temporal patterning involves the sequential expression of transcription factors (TFs) in neural progenitors to diversify neuronal identity, in part through the initial expression of homeodomain TF combinations. Here, we address the role of the Drosophila temporal TF Hunchback and the homeodomain TF Bicoid in the assembly of the Pair1 (SEZ_DN1) descending neuron locomotor circuit, which promotes larval pausing and head casting. We find that both Hunchback and Bicoid are expressed in larval Pair1 neurons, Hunchback activates Bicoid in Pair1 (opposite of their embryonic relationship), and the loss of Hunchback function or Bicoid function from Pair1 leads to ectopic presynapse numbers in Pair1 axons and an increase in Pair1-induced pausing behavior. These phenotypes are highly specific, as the loss of Bicoid or Hunchback has no effect on Pair1 neurotransmitter identity, dendrite morphology, or axonal morphology. Importantly, the loss of Hunchback or Bicoid in Pair1 leads to the addition of new circuit partners that may underlie the exaggerated locomotor pausing behavior. These data are the first to show a role for Bicoid outside of embryonic patterning and the first to demonstrate a cell-autonomous role for Hunchback and Bicoid in interneuron synapse targeting and locomotor behavior.

Developmental origin of the Pair1 descending interneuron.

Pair1 is part of a Drosophila larval locomotor circuit that promotes backward locomotion by inhibiting forward locomotion. We hypothesize that lineage related neurons may function in neuronal circuits together. Testing this hypothesis requires knowing the progenitor of each neuron within this locomotor circuit, and here we focus exclusively on Pair1. During Drosophila melanogaster embryogenesis, unique neuroblasts form by inheriting the spatial transcription factors (TFs) expressed in their birth location within the neuroectoderm. We examine the Pair1 neurons using immunofluorescence to determine which neuroblast the Pair1s derive from. Our results show that Pair1 is derived from gnathal neuroblast 5-3 which expresses Gooseberry (Gsb) and Intermediate neuroblasts defective (Ind). When Gsb or Ind were overexpressed in the Pair1 lineage, extra neurons formed with similar Pair1 morphology.