Abstract
Proper somatosensory circuit assembly is critical for processing somatosensory stimuli and for responding accordingly. In comparison to other sensory circuits (e.g., olfactory and visual), somatosensory circuits have unique anatomy and function. However, understanding of somatosensory circuit development lags far behind that of other sensory systems. For example, there are few identified transcription factors required for integration of interneurons into functional somatosensory circuits. Here, as a model, we examine one type of somatosensory interneuron, Even-skipped expressing Laterally placed interneurons (ELs) of the Drosophila larval nerve cord. Even-skipped (Eve) is a highly conserved, homeodomain transcription factor known to play a role in cell fate specification and neuronal axon guidance. Because marker genes are often functionally important in the cell types they define, we deleted eve specifically from EL interneurons. On the cell biological level, using single neuron labeling, we find eve plays several previously undescribed roles in refinement of neuron morphogenesis. Eve suppresses aberrant neurite branching, promotes axon elongation, and regulates dorsal-ventral dendrite position. On the circuit level, using optogenetics, calcium imaging, and behavioral analysis, we find eve is required in EL interneurons for the normal encoding of somatosensory stimuli and for normal mapping of outputs to behavior. We conclude that eve coordinately regulates multiple aspects of EL interneuron morphogenesis and is critically required to properly integrate EL interneurons into somatosensory circuits. Our data shed light on the genetic regulation of somatosensory circuit assembly.
Significance statement
In general, even-skipped (eve) genes are considered neural cell fate determinants. Here, we show that eve is required for refinement of axon and dendrite morphogenesis and for proper functional integration of neurons into somatosensory circuits. Thus, eve coordinately regulates multiple terminal neuronal features of a class of Eve-expressing interneurons, raising the possibility that, in other neuronal contexts, eve genes regulate a similar suite of features. Our study pushes the understanding of eve beyond the level of neuron morphology to the levels of circuit physiology and whole animal behavior. It thereby provides an updated understanding of eve in development. Further, our data identify eve as a genetic entry point for future study of sensorimotor circuit assembly in Drosophila.
Footnotes
The authors declare no competing financial interests.
NIH grant R01-NS105748 University of Chicago, Department of Molecular Genetics and Cell Biology Start-up funds to ESH.
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
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