A step-by-step guide to visual circuit assembly in Drosophila
Introduction
In the visual system of vertebrates and insects, reiterated columnar mini-circuits process the information from defined points in space and form the building blocks of a continuous retinotopic map that covers the entire visual field. In addition, layer-specific synaptic connections provide the structural basis for parallel information processing of distinct visual features, such as motion and spectral sensitivity. How these synaptic units are assembled during development is a fundamental and fascinating question. In Drosophila, an expanding repertoire of genetic tools and markers made it increasingly possible to precisely break down the temporal sequence of the developmentally regulated steps that underlie the formation of a functional visual system. In this review, we will summarize our current understanding of the molecular programs that direct visual circuit formation in flies and highlight the general developmental principles that have emerged over the past years through studies of this model system.
Section snippets
Visual system organization into columnar and layered circuits
The Drosophila retina consists of approximately 750 ommatidia, each containing 8 photoreceptor subtypes (R-cells, R1–R8). R1–R6 cells mediate motion detection and express rhodopsin 1 (Rh1), which is sensitive to a broad spectrum of visible light. Photoreceptors R8 and R7 are specialized for color and polarized light detection and express the blue and green light-sensitive rhodopsins Rh5 and Rh6, and the ultraviolet light-sensitive rhodopsins Rh3 and Rh4, respectively [1]. R-cell axons project
Retinotopic map formation in the 3rd instar larval optic lobe
In the developing visual system, neurogenesis and gliogenesis are tightly linked with connectivity, and both involve interactions between R-cell axons, glia and target neurons. At the 3rd instar larval stage, R-cells differentiate and assemble into rows of ommatidial clusters and extend axons into the optic lobe in a defined temporal order [9, 10••] (Figure 2a). R-cells majorly influence optic lobe development, as each of their ingrowing axon bundles induces the formation and differentiation of
Finding synaptic partners in lamina cartridges
Due to the curvature and structure of the adult eye, R-cells within one ommatidium have different optical axes. As a result, six neighboring ommatidia contain one R-cell of each subtype that share the same orientation [26, 27, 28]. Larval R1–R6 axons from each ommatidial cluster initially project as one bundle into the lamina and are associated with one set of lamina neurons in a column (Figure 3). Within a narrow time window during early pupal development, growth cones leave their original
Targeting to layers and columns in the medulla
Larval R8 and R7 axons extend through the lamina and initially project closely adjacent to each other into the medulla neuropil. During pupal development R8 and R7 axons target to their final synaptic layers in a two-step layer selection process [35] (Figure 4a). Initially, R8 axons pause in a temporary layer at the distal medulla neuropil border, while R7 axons transiently target to a deeper layer in the medulla. R8 and R7 growth cones adopt these positions actively and in part due to
Conclusions and future directions
Together, the outlined studies show that wiring of the fly visual system is achieved through the coordinated execution of multiple interdependent, cell-type-specific programs during larval and pupal stages. Sophisticated genetic screens for visually driven behaviors have facilitated the discovery of key determinants required for R-cell axon targeting. Conversely, disrupting the connectivity during development has proven instrumental for gaining insights into the underlying neuronal basis of
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
We would like to apologize to those of our colleagues, whose work was not included in this review because of space constraints. We thank Holger Apitz, Emily Richardson, Benjamin Richier, and Nana Shimosako for critically reading the manuscript. KT, DH, and IS are supported by the Medical Research Council (U117581332).
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