Spatio-temporal relays control layer identity of direction-selective neuron subtypes in Drosophila

Abstract

Visual motion detection in sighted animals is essential to guide behavioral actions ensuring their survival. In Drosophila, motion direction is first detected by T4/T5 neurons. Their axons innervate one of the four lobula plate layers. How T4/T5 neurons with layer-specific representation of motion-direction preferences are specified during development is unknown. We show that diffusible Wingless (Wg) between adjacent neuroepithelia induces its own expression to form secondary signaling centers. These activate Decapentaplegic (Dpp) signaling in adjacent lateral tertiary neuroepithelial domains dedicated to producing layer 3/4-specific T4/T5 neurons. T4/T5 neurons derived from the core domain devoid of Dpp signaling adopt the default layer 1/2 fate. Dpp signaling induces the expression of the T-box transcription factor Optomotor-blind (Omb), serving as a relay to postmitotic neurons. Omb-mediated repression of Dachshund transforms layer 1/2- into layer 3/4-specific neurons. Hence, spatio-temporal relay mechanisms, bridging the distances between neuroepithelial domains and their postmitotic progeny, implement T4/T5 neuron-subtype identity.

A combinatorial code of transcription factors specifies subtypes of visual motion-sensing neurons in Drosophila

“…Consistent with our scRNAseq analysis, a previous study found dac and omb to be expressed in postmitotic, developing T4/T5a,b and T4/T5c,d neurons, respectively (Fig. 4B,E) (Apitz and Salecker, 2018). Our scRNA-seq analysis further revealed that ab was specific to T4/T5a,b (Fig.…”

“…Based on the previously reported subtype-specific marker genes optomotor-blind (omb) and dachshund (dac) (Apitz and Salecker, 2018), we assigned clusters to one of the following subtype-pairs: T4a,b, T5a,b, T4c,d or T5c,d (Fig. 3B, Fig.…”

“…Spatial patterning of the neuroepithelium that generates T4/T5-producing neuroblasts results in the specific expression of omb in neuroblasts that are precursors of T4/T5c,d neurons. Omb expression is further relayed to postmitotic, developing T4/T5c,d neurons, in which it represses dac expression (Apitz and Salecker, 2018). In addition, each Ombneuroblast (precursor of T4/T5a,b), as well as each Omb + neuroblast (precursor of T4/T5c,d), divides to produce two ganglion mother cells; only one of them with Notch activity.…”

“…Recent studies have uncovered the developmental genetic programs that drive the specification of T4/T5 neurons into the four subtypes (Apitz and Salecker, 2018;Pinto-Teixeira et al, 2018). During the differentiation of postmitotic T4/T5 neurons, these programs must be translated into the expression of effector genes ensuring that four subgroups of T4 and T5 neurons develop dendrites oriented along four different directions in common extracellular environments.…”

“…1A). Until now, only one gene (optomotor-blind) has been proposed to act in differentiating T4/T5c,d to distinguish their axons from those of T4/T5a,b neurons (Apitz and Salecker, 2018). Therefore, the following questions have remained elusive so far: (1) How do axons of T4/T5a and T4/T5b or axons of T4/T5c and T4/T5d become distinct from each other?, (2) How do the four T4/T5 subtypes acquire their four different dendrite orientations?, and (3) How is dendrite orientation matched to axon projection layer within each subtype?…”