A step-by-step guide to visual circuit assembly in Drosophila

https://doi.org/10.1016/j.conb.2010.07.012Get rights and content

The ability of vertebrates and insects to perceive and process information about the visual world is mediated by neural circuits, which share a strikingly conserved architecture of reiterated columnar and layered synaptic units. Recent genetic approaches conferring single-cell resolution have enabled major advances in our understanding of the cellular and molecular strategies that orchestrate visual circuit assembly in Drosophila. Photoreceptor axon targeting relies on a sequence of interdependent developmental steps to achieve temporal coordination with the formation and maturation of partner neurons. Distinct targeting events depend on anterograde and autocrine signaling, neuron–glia interactions, axon tiling and the timely expression of homophilic cell surface molecules. These mediate local adhesive or repulsive interactions of photoreceptor axons with each other and with target neurons.

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).

References (55)

  • T.R. Clandinin et al.

    Afferent growth cone interactions control synaptic specificity in the Drosophila visual system

    Neuron

    (2000)
  • S. Prakash et al.

    Drosophila N-cadherin mediates an attractive interaction between photoreceptor axons and their targets

    Nat Neurosci

    (2005)
  • K.M. Choe et al.

    Liprin-alpha is required for photoreceptor target selection in Drosophila

    Proc Natl Acad Sci U S A

    (2006)
  • C.Y. Ting et al.

    Drosophila N-cadherin functions in the first stage of the two-stage layer-selection process of R7 photoreceptor afferents

    Development

    (2005)
  • A. Nern et al.

    Local N-cadherin interactions mediate distinct steps in the targeting of lamina neurons

    Neuron

    (2008)
  • M. Shinza-Kameda et al.

    Regulation of layer-specific targeting by reciprocal expression of a cell adhesion molecule, capricious

    Neuron

    (2006)
  • E. Bazigou et al.

    Anterograde Jelly belly and Alk receptor tyrosine kinase signaling mediates retinal axon targeting in Drosophila

    Cell

    (2007)
  • T.P. Newsome et al.

    Analysis of Drosophila photoreceptor axon guidance in eye-specific mosaics

    Development

    (2000)
  • C. Maurel-Zaffran et al.

    Cell-autonomous and -nonautonomous functions of LAR in R7 photoreceptor axon targeting

    Neuron

    (2001)
  • C.Y. Ting et al.

    Tiling of R7 axons in the Drosophila visual system is mediated both by transduction of an activin signal to the nucleus and by mutual repulsion

    Neuron

    (2007)
  • M. Morey et al.

    Coordinate control of synaptic-layer specificity and rhodopsins in photoreceptor neurons

    Nature

    (2008)
  • P.R. Hiesinger et al.

    Activity-independent prespecification of synaptic partners in the visual map of Drosophila

    Curr Biol

    (2006)
  • J. Rister et al.

    Dissection of the peripheral motion channel in the visual system of Drosophila melanogaster

    Neuron

    (2007)
  • I.A. Meinertzhagen et al.

    The development of the optic lobe

  • K.F. Fischbach et al.

    The optic lobe of Drosophila melanogaster. I. A Golgi analysis of wild-type structure

    Cell Tissue Res

    (1989)
  • I.A. Meinertzhagen et al.

    Synaptic organization of columnar elements in the lamina of the wild type in Drosophila melanogaster

    J Comp Neurol

    (1991)
  • S.Y. Takemura et al.

    Synaptic circuits of the Drosophila optic lobe: the input terminals to the medulla

    J Comp Neurol

    (2008)
  • Cited by (66)

    • Ataxin-2 is essential for cytoskeletal dynamics and neurodevelopment in Drosophila

      2022, iScience
      Citation Excerpt :

      Quantification of the brain lobes (Figure 4J, cyan) showed a roughly 2-fold decrease in area (Figure 4K). Further, we quantified the area of the retinotopic pattern—the structure representing the photoreceptor axons (Figure 4J, magenta) (Hadjieconomou et al., 2011). When normalized to the area of the brain lobe, we found this structure was decreased to around 10% of control area upon Atx2 depletion (Figure 4L).

    • Spatio-temporal pattern of neuronal differentiation in the Drosophila visual system: A user's guide to the dynamic morphology of the developing optic lobe

      2017, Developmental Biology
      Citation Excerpt :

      The optic lobe of the adult fly has four main compartments (“optic ganglia”), the lamina, medulla, lobula and lobula plate (Fig. 1). Photoreceptors involved in motion detection (R1-6) terminate in the lamina; R7 and R8, responsible for color vision, project to the outer medulla (Hadjieconomou et al., 2011; Meinertzhagen and Hanson, 1993; Braitenberg, 1967; Trujillo-Cenóz, 1965). This ordered projection subdivides the lamina and medulla into stereotyped, repetitive units, called cartridges in the lamina and columns in the medulla (Fig. 1).

    View all citing articles on Scopus
    View full text