Unc-4 acts to promote neuronal identity and development of the take-off circuit in the Drosophila CNS.

Haluk Lacin,Gwyneth M Card,W Ryan Williamson,James W Truman,James B Skeath

doi:10.7554/elife.55007

Abstract

The Drosophila ventral nerve cord (VNC) is composed of thousands of neurons born from a set of individually identifiable stem cells. The VNC harbors neuronal circuits required to execute key behaviors, such as flying and walking. Leveraging the lineage-based functional organization of the VNC, we investigated the developmental and molecular basis of behavior by focusing on lineage-specific functions of the homeodomain transcription factor, Unc-4. We found that Unc-4 functions in lineage 11A to promote cholinergic neurotransmitter identity and suppress the GABA fate. In lineage 7B, Unc-4 promotes proper neuronal projections to the leg neuropil and a specific flight-related take-off behavior. We also uncovered that Unc-4 acts peripherally to promote proprioceptive sensory organ development and the execution of specific leg-related behaviors. Through time-dependent conditional knock-out of Unc-4, we found that its function is required during development, but not in the adult, to regulate the above events.

Highlights

How does a complex nervous system arise during development? Millions to billions of neurons, each one essentially unique, precisely interconnect to create a functional central nervous system (CNS) that drives animal behavior (HERCULANO-HOUZEL 2009)
Using precise genetic tools, we dissected the function of the Unc-4 transcription factor in a lineagespecific manner
We found that within the peripheral nervous system (PNS), Unc-4 function is needed for the proper development of the FeCo likely leading to an impairment of walking; whereas in the CNS, Unc-4 dictates neurotransmitter usage within lineage 11A and regulates axonal projection and flight takeoff behavior in lineage 7B

Summary

INTRODUCTION

How does a complex nervous system arise during development? Millions to billions of neurons, each one essentially unique, precisely interconnect to create a functional central nervous system (CNS) that drives animal behavior (HERCULANO-HOUZEL 2009). We previously mapped the embryonic origin, axonal projection pattern, transcription factor expression, and neurotransmitter usage of essentially all hemilineages in the adult Drosophila VNC (TRUMAN et al 2004; TRUMAN et al 2010; LACIN et al 2014; HARRIS et al 2015; LACIN AND TRUMAN 2016; SHEPHERD et al 2016; LACIN et al 2019; SHEPHERD et al 2019) We leverage this information to elucidate how a specific transcription factor, Unc-4, acts within individual hemilineages during adult nervous system development to regulate neuronal connectivity and function, and animal behavior. We find that Unc-4 is expressed in the precursors of chordotonal sensory neurons and required for the development of these sensory organs, with functional data indicating Unc-4 functions in this lineage to promote climbing, walking, and grooming activities

RESULTS

DISCUSSION

MATERIALS & METHODS