Drosophila Eye Development and Photoreceptor Specification

Abstract

The compound eye of the fruitfly Drosophila melanogaster is composed of 800 unit eyes called ommatidia, which are composed of eight neural photoreceptor cells and 12 supporting cells. All these cells are generated from an epithelial sheet called the eye imaginal disc through sequential specification and differentiation achieved by the spatially and temporally restricted expression of transcription factors and signalling pathways. Many of these factors and signals and their mode of action have been identified in recent years. Here, the authors give a brief overview of the molecular pathways that play major roles in photoreceptor specification and their terminal differentiation. Thus, the fly eye has provided important data to current understanding of developmental signalling processes and the specification of neural cell types, their patterning and structure and thus represents one of the most powerful genetic model systems for studying nervous system development.

Key Concepts:

  • The Drosophila eye is a highly preferred model system to dissect molecular interactions and developmental mechanisms of the nervous system.

  • It consists of ∼800 units called ommatidia; each has eight neural (photoreceptors) and 12 non‐neural (cone, pigment and bristle) cells.

  • The Drosophila eye emerges during late larval and pupal stage, from a monolayer epithelium called the eye‐antenna imaginal disc.

  • The morphogenetic furrow is a wave of differentiation sweeping across the eye imaginal disc from posterior to anterior initiating sequential differentiation at each line of cells it passes.

  • The morphogenetic furrow is initiated and pushed by a Hedgehog signal; this short‐range signal induces a long‐range Dpp signal to induce neurogenesis via Atonal, while the Dpp signal is suppressed by a Wingless signal secreted from the anterior margin of the eye imaginal disc.

  • Once the Morphogenetic Furrow passes a point in the eye imaginal disc, it creates a cluster of proneural cells resembling rosettes; a single cell out of this cluster is selected to become the the founder cell, R8. The rest of the photoreceptor cells are specified with the help of R8, using a network of molecular interactions.

  • During the development of the retina, the cellular cytoskeleton and cell–cell junctions are actively reorganised.

  • Although the outer photoreceptors (R1–R6) express dim light‐sensitive rhodopsin Rh1, the inner photoreceptors 7 express either UV‐sensitive rhodopsin Rh3 or rhodopsin Rh4, where the blue‐sensitive rhodopsin Rh5 is always accompanied with Rh6 in photoreceptor 8.

  • Sequential activation of different transcription factors leads to regional or stochastic determination of photoreceptor subtypes.

Keywords: eye development; compound eye; eye imaginal disc; morphogenetic furrow; retinal determination genes; molecular signaling; pattern generation; photoreceptor specification; rhodopsin; terminal differentiation

Figure 1.

Organisation and development of retinal cells. (a) Transverse section of the distal half of an adult ommatidium. Six outer PRs and one of the inner PRs are visible. PRs specified simultaneously are represented in the same colour. R3 rhabdomere is located further apart from the inner PR, giving rise to a trapezoid shape. Rhabdomeres are shown in dark grey. Secondary and tertiary pigment cells surround the PRs. Bristle cells are localised evenly. (b) Longitudinal section of an adult ommatidium, distal side up. Each ommatidium is covered by an individual lens and a pseudo‐cone, which are secreted by the four cone cells. R7 cells sit on top of the R8 cell (only the rhabdomeres are shown in the section). (c) The eye‐antennal imaginal disc is a continuous tissue, where the posterior part gives rise to the eye and the anterior part gives rise to the antenna and maxillary palps. The morphogenetic furrow (MF, indicated with blue), moves from the posterior (P) to the anterior (A). Its progression is antagonised by Wingless (Wg) secreted from anterio‐lateral margins of the eye disc. The inset shows differential gene expression at the MF. The MF is indicated in dark blue. The cells after the MF express Atonal (Ato, pink) and start differentiation. Behind the MF, proneurogenesis starts at the 3–4 columns of cell, shown with a purple arrowhead. Starting immediately after the MF, Hedgehog (Hh) is secreted. The cells immediately anterior to the MF receive the Hh signal in a gradually decreasing fashion and respond by secreting Decapentaplegic (Dpp). An appropriate level of Dpp is required to start proneurogenesis. Dpp levels decrease gradually from posterior to anterior, whereby its activity is also antagonised by the Wg gradient decreasing anterior to posterior. This limits the future cells that will start proneurogenesis to a thin line of cells. (d) A simplified interaction scheme for MF progression. Expression of proneural factor Ato is controlled by several factors to enable proper initiation of ommatidial assembly. Reprinted with permission from Wolff and Ready . © Cold Spring Harbor Laboratory Press.

Figure 2.

Sequential assembly of ommatidia. The same colour code with Figure is used for the retinal cell types. The eye disc is symmetrical around the equator. The polarisation of cells along an epithelial sheet is known as PCP. Immediately behind the MF, clusters of cells called ‘rosettes’ assemble (not shown). One cell per rosette expresses Ato and acquires the R8 fate. Along the specification process all the PRs express Ato to start proneurogenesis. Later R8 cells express Senseless (Sens). R2/R5, specified from the rosette, expresses Rough (Ro). R3/R4 also recruited from the rosettes express Seven‐up (Svp) following expression of Ro. From these two cells, the one expressing Frizzled (Fz), which is always localised closer to the equator, will form R3, and the other will form R4. R1/R6 and R7 are recruited from the cells that have passed the second mitotic wave. R1/R6 expresses Lozenge (Lz) in addition to Svp, and R7 expresses Prospero (Pros) in addition to Lz. Posterior is to the right, dorsal is towards the top.

Figure 3.

Dorso–ventral specification of the eye disc. Dorsal and ventral identities in the eye imaginal disc are established in early larval stages. The border between the two halves, called midline can be recognised by Notch (N) expression. The Notch ligand Serrate (Ser) is expressed on the ventral side, and Delta (Dl) in the dorsal side. Fringe (Fng) is known to modulate Notch activity by modifying the Notch protein. A simplified scheme of the Notch pathway members and Wingless (Wg), Homothorax (Hth), Teashirt (Tsh), Iroquois (Iro‐C), Extradenticle (Exd), Lobe (L), and Pannier (Pnr) molecules are represented. Although some molecules like Fng and Ser are expressed in both halves, for the sake of simplicity they are shown only in the half where they exert a specific role.

Figure 4.

Early development of the eye. The same colour code is used for the retinal cell types as in Figure and Figure. The apical surface of the early photoreceptors fold inside during the mid‐pupal stage, to form the rhabdomere. Photoreceptors attach to each other with Zonula adherens junctions, which also change polarity and extend to the basal side, along the PRs; whereas, pigment cells do not change their apico–basal polarity.

Figure 5.

Rh choice and establishment of retinal subtypes. (a) Spalt (Sal) acts to generate a generic inner PR fate, while specific expression of Prospero (Pros) and Senseless (sens) helps to distinguish R7 and R8 fate, respectively. Homothorax (Hth) in turn commits inner PRs to the Drosal Rim Area (DRA) fate. Orthodenticle (Otd) helps in the establishment of the pale (p) fate while Spineless (Ss) establishes the yellow (y) fate. Expression of Iroquois Complex (Iro‐C) in the dorsal‐most part of the retina leads to the ‘dorsal yellow’ fate. (b) The 30% Rh3: 70% Rh4 ratio is generated in the R7 cell by Ss leading to the expression of rh4 cells and the repression of rh3 by Defective proventriculus (Dve) in yellow R7. In 30% of the cells rh3 will be expressed because of lack of Ss and Dve and presence of Otd. Expression of Iro‐C in the dorsal third of the retina will lead to the de‐repression of rh3 in rh4‐expressing yellow R7 cells by overriding the repression through Dve. The choice of Rh expression in the R7 cells is communicated to the underlying R8 cells from the pale R7 to the pale R8. The nature of the signal is not known, but is received in the pR8 by the PH‐domain protein Melted (Melt). Expression of melted will lead to the repression of Large tumour suppressor (Lats) and the expression of rh5. Yellow R8 that do not receive a signal will express Lats, which in turn will repress melt expression and ultimately lead to the expression of rh6.

close

References

Baker NE and Firth LC (2011) Retinal determination genes function along with cell–cell signals to regulate Drosophila eye development: examples of multi‐layered regulation by master regulators. Bioessays 33(7): 538–546.

Bao S (2010) Two themes on the assembly of the Drosophila eye. Current Topics in Developmental Biology 93: 85–127.

Cook T, Pichaud F, Sonneville R, Papatsenko D and Desplan C (2003) Distinction between color photoreceptor cell fates is controlled by Prospero in Drosophila. Developmental Cell 4(6): 853–864.

Johnston RJ Jr, Otake Y, Sood P et al. (2011) Interlocked feedforward loops control cell‐type‐specific Rhodopsin expression in the Drosophila eye. Cell 145(6): 956–968.

Jukam D and Desplan C (2011) Binary regulation of Hippo pathway by Merlin/NF2, Kibra, Lgl, and Melted specifies and maintains postmitotic neuronal fate. Developmental Cell 21(5): 874–887.

Kumar JP (2012) Building an ommatidium one cell at a time. Developmental Dynamics 241(1): 136–149.

Lopes CS and Casares F (2010) Hth maintains the pool of eye progenitors and its downregulation by Dpp and Hh couples retinal fate acquisition with cell cycle exit. Developmental Biology 339(1): 78–88.

Mazzoni EO, Celik A, Wernet MF et al. (2007) Iroquois complex genes induce co‐expression of rhodopsins in Drosophila. PLoS Biolgy 6(4): e97.

Mikeladze‐Dvali T, Wernet MF, Pistillo D et al. (2005) The growth regulators warts/lats and melted interact in a bistable loop to specify opposite fates in Drosophila R8 photoreceptors. Cell 122(5): 775–787.

Tahayato A, Sonneville R, Pichaud F et al. (2003) Otd/Crx, a dual regulator for the specification of ommatidia subtypes in the Drosophila retina. Developmental Cell 5(3): 391–402.

Tsachaki M and Sprecher SG (2012) Genetic and developmental mechanisms underlying the formation of the Drosophila compound eye. Developmental Dynamics 241(1): 40–56.

Vasiliauskas D, Mazzoni EO, Sprecher SG et al. (2011) Feedback from rhodopsin controls rhodopsin exclusion in Drosophila photoreceptors. Nature 479(7371): 108–112.

Wernet MF, Labhart T, Baumann F et al. (2003) Homothorax switches function of Drosophila photoreceptors from color to polarized light sensors. Cell 115(3): 267–279.

Wernet MF, Mazzoni EO, Celik A et al. (2006) Stochastic spineless expression creates the retinal mosaic for colour vision. Nature 440(7081): 174–180.

Wolff T and Ready DF (1993) The Development of Drosophila Melanogaster, Pattern formation in the Drosophila retina, p. 1280. Plainview, NY: Cold Spring Harbor Laboratory Press.

Xie B, Charlton‐Perkins M, McDonald E, Gebelein B and Cook T (2007) Senseless functions as a molecular switch for color photoreceptor differentiation in Drosophila. Development 134(23): 4243–4253.

Further Reading

Charlton‐Perkins M and Cook TA (2010) Building a fly eye: terminal differentiation events of the retina, corneal lens, and pigmented epithelia. Current Topics in Developmental Biology 93: 129–173.

Cook T and Desplan C (2001) Photoreceptor subtype specification: from flies to humans. Seminars in Cell and Developmental Biology 12(6): 509–518.

O'Kane CJ (2003) Modelling human diseases in Drosophila and Caenorhabditis. Seminars in Cell and Developmental Biology 14(1): 3–10.

Quan XJ, Ramaekers A and Hassan BA (2012) Transcriptional control of cell fate specification: lessons from the fly retina. Current Topics in Developmental Biology 98: 259–276.

Singh A, Tare M, Puli OR and Kango‐Singh M (2012) A glimpse into dorso–ventral patterning of the Drosophila eye. Developmental Dynamics 241(1): 69–84.

Tepass U and Harris KP (2007) Adherens junctions in Drosophila retinal morphogenesis. Trends in Cell Biology 17(1): 26–35.

Thomas C and Strutt D (2012) The roles of the cadherins Fat and Dachsous in planar polarity specification in Drosophila. Developmental Dynamics 241(1): 27–39.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Şahin, H Bahar, and Çelik, Arzu(Mar 2013) Drosophila Eye Development and Photoreceptor Specification. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001147.pub2]