Faculty Bibliography

To navigate through the environment, animals rely on visual feedback to control their movements relative to their surroundings. In dipteran flies, visual feedback is provided by the wide-field motion-sensitive neurons in the visual system called lobula plate tangential cells (LPTCs). Understanding the role of LPTCs in fly behaviors can address many fundamental questions on how sensory circuits guide behaviors. The blowfly was estimated to have ~ 60 LPTCs, but only a few have been identified in Drosophila. We conducted a Gal4 driver screen and identified five LPTC subtypes in Drosophila, based on their morphological characteristics: LPTCs have large arborizations in the lobula plate and project to the central brain. We compared their morphologies to the blowfly LPTCs and named them after the most similar blowfly cells: CH, H1, H2, FD1 and FD3, and V1. We further characterized their pre- and post-synaptic organizations, as well as their neurotransmitter profiles. These anatomical features largely agree with the anatomy and function of their likely blowfly counterparts. Nevertheless, several anatomical details indicate the Drosophila LPTCs may have more complex functions. Our characterization of these five LPTCs in Drosophila will facilitate further functional studies to understand their roles in the visual circuits that instruct fly behaviors.

Animals rely on their chemosensory system to discriminate among a very large number of attractive or repulsive chemical cues in the environment, which is essential to respond with proper action. The olfactory sensory systems in insects share significant similarities with those of vertebrates, although they also exhibit dramatic differences, such as the molecular nature of the odorant receptors (ORs): insect ORs function as heteromeric ion channels with a common Orco subunit, unlike the G-protein-coupled olfactory receptors found in vertebrates. Remarkable progress has recently been made in understanding the evolution, development and function of insect odorant receptor neurons (ORNs). These studies have uncovered the diversity of olfactory sensory systems among insect species, including in eusocial insects that rely extensively on olfactory sensing of pheromones for social communication. However, further studies, notably functional analyses, are needed to improve our understanding of the origins of the Orco-OR system, the mechanisms of ORN fate determination, and the extraordinary diversity of behavioral responses to chemical cues.

The Drosophila visual system integrates input from 800 ommatidia and extracts different features in stereotypically connected optic ganglia. The development of the Drosophila visual system is controlled by gene regulatory networks that control the number of precursor cells, generate neuronal diversity by integrating spatial and temporal information, coordinate the timing of retinal and optic lobe cell differentiation, and determine distinct synaptic targets of each cell type. In this chapter, we describe the known gene regulatory networks involved in the development of the different parts of the visual system and explore general components in these gene networks. Finally, we discuss the advantages of the fly visual system as a model for gene regulatory network discovery in the era of single-cell transcriptomics.

Sensory systems use stochastic fate specification to increase their repertoire of neuronal types. How these stochastic decisions are coordinated with the development of their targets is unknown. In the Drosophila retina, two subtypes of UV-sensitive R7-photoreceptors are stochastically specified. In contrast, their targets in the brain are specified through a deterministic program. Here, we identify subtypes of the main target of R7, the Dm8 neurons, each specific to the different subtypes of R7s. Dm8 subtypes are produced in excess by distinct neuronal progenitors, independently from R7. Following matching with their cognate R7, supernumerary Dm8s are eliminated by apoptosis. Two interacting cell adhesion molecules, Dpr11 and DIPγ, are essential for the matching of one of the synaptic pairs. These mechanisms allow the qualitative and quantitative matching of R7/Dm8 and permit the stochastic choice made in R7 to propagate to the brain.

Precise formation of neuronal circuits requires the coordinated development of the different components of the circuit. Here, we review examples of coordination at multiples scales of development in one of the best-studied systems for neural patterning and circuit assembly, the Drosophila visual system, from coordination of gene expression in photoreceptors to the coordinated patterning of the different neuropiles of the optic lobe.

A genetic pathway that times development works together with the sex-determination pathway to control the timing of sexually dimorphic neural development in C. elegans.

Eusocial insects live in societies in which distinct family members serve specific roles in maintaining the colony and advancing the reproductive ability of a few select individuals. Given the genetic similarity of all colony members, the diversity of morphologies and behaviors is surprising. Social communication relies on pheromones and olfaction, as shown by mutants of orco, the universal odorant receptor coreceptor, and through electrophysiological analysis of neuronal responses to pheromones. Additionally, neurohormonal factors and epigenetic regulators play a key role in caste-specific behavior, such as foraging and caste switching. These studies start to allow an understanding of the molecular mechanisms underlying social behavior and provide a technological foundation for future studies of eusocial insects. In this review, we highlight recent findings in eusocial insects that advance our understanding of genetic and epigenetic regulations of social behavior and provide perspectives on future studies using cutting-edge technologies. Expected final online publication date for the Annual Review of Genetics Volume 52 is November 23, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

While most processes in biology are highly deterministic, stochastic mechanisms are sometimes used to increase cellular diversity. In human and Drosophila eyes, photoreceptors sensitive to different wavelengths of light are distributed in stochastic patterns, and one such patterning system has been analyzed in detail in the Drosophila retina. Interestingly, some species in the dipteran family Dolichopodidae (the "long legged" flies, or "Doli") instead exhibit highly orderly deterministic eye patterns. In these species, alternating columns of ommatidia (unit eyes) produce corneal lenses of different colors. Occasional perturbations in some individuals disrupt the regular columns in a way that suggests that patterning occurs via a posterior-to-anterior signaling relay during development, and that specification follows a local, cellular-automaton-like rule. We hypothesize that the regulatory mechanisms that pattern the eye are largely conserved among flies and that the difference between unordered Drosophila and ordered dolichopodid eyes can be explained in terms of relative strengths of signaling interactions rather than a rewiring of the regulatory network itself. We present a simple stochastic model that is capable of explaining both the stochastic Drosophila eye and the striped pattern of Dolichopodidae eyes and thereby characterize the least number of underlying developmental rules necessary to produce both stochastic and deterministic patterns. We show that only small changes to model parameters are needed to also reproduce intermediate, semi-random patterns observed in another Doli species, and quantification of ommatidial distributions in these eyes suggests that their patterning follows similar rules.

To understand how neurons assemble to form functional circuits, it is necessary to obtain a detailed knowledge of their diversity and to define the developmental specification programs that give rise to this diversity. Invertebrates and vertebrates appear to share common developmental principles of neuronal specification in which cascades of transcription factors temporally pattern progenitors, while spatial cues modify the outcomes of this temporal patterning. Here, we highlight these conserved mechanisms and describe how they are used in distinct neural structures. We present the questions that remain for a better understanding of neuronal specification. Single-cell RNA profiling approaches will potentially shed light on these questions, allowing not only the characterization of neuronal diversity in adult brains, but also the investigation of the developmental trajectories leading to the generation and maintenance of this diversity.