A Conserved Developmental Mechanism Builds Complex Visual Systems in Insects and Vertebrates

Abstract

The visual systems of vertebrates and many other bilaterian clades consist of complex neural structures guiding a wide spectrum of behaviors. Homologies at the level of cell types and even discrete neural circuits have been proposed, but many questions of how the architecture of visual neuropils evolved among different phyla remain open. In this review we argue that the profound conservation of genetic and developmental steps generating the eye and its target neuropils in fish and fruit flies supports a homology between some core elements of bilaterian visual circuitries. Fish retina and tectum, and fly optic lobe, develop from a partitioned, unidirectionally proliferating neurectodermal domain that combines slowly dividing neuroepithelial stem cells and rapidly amplifying progenitors with shared genetic signatures to generate large numbers and different types of neurons in a temporally ordered way. This peculiar 'conveyor belt neurogenesis' could play an essential role in generating the topographically ordered circuitry of the visual system.

Figure 1. Schematic representation of the visual neuropil layers and their connectivity in zebrafish and Drosophila

A strict retinotopic organization of the visual neuropils is maintained throughout all layers of the retina to the optic tectum in vertebrates, and throughout all neuropils of the optic lobe in Drosophila.

Figure 2. Embryonic origin and morphogenesis of the visual system in zebrafish and Drosophila

(A) Schematic of zebrafish late gastrula/early neurula embryo, dorsal view (redrawn from [74]). The domains giving rise to the optic tectum and neural retina fall within the Otx-positive anterior neural plate. The anlage of the retina (eye field) is characterized by the expression of Pax6, Six1/3/6 and Rx. Grey transverse stripe posterior to the tectum indicates the midbrain–hindbrain boundary, which expresses Pax2/5/8 and Engrailed (En). (B) Fatemap of the Drosophila visual system at the gastrula stage. Otd defines a large domain within the dorso-anterior neurectoderm that gives rise to the protocerebrum and visual system. The Six1 homolog Sine oculis (So) and the Pax6 homolog Twin of eyeless (Toy) are expressed in the anlage of the visual system, which includes the eye and optic lobe. Expression of the Pax2/5/8 homologs Poxn and Dpax2 are observed in a narrow stripe of neurectoderm likened to the vertebrate midbrain– hindbrain boundary [21]. Similar medio-lateral systems (medial: Vnd/Nkx; intermediate: Ind/Gsx (stippled); lateral: Msh/Msx) subdivide the neurectoderm in fish and flies. Drosophila Ind expression overlaps with the anterior lip of the optic lobe anlage, which gives rise to the lobula complex, while the zebrafish Ind homolog, Gsx, is expressed in the optic tectum. (C) Zebrafish brain and visual system at larval stage, lateral view (anterior to the left). (D,E) Lateral view of late Drosophila embryo (D) and 24 h pupa (E), depicting the protocerebrum and associated visual system. Consistent color code used throughout (A–E) illustrates the relationship between early embryonic anlagen and their derivatives.

Figure 3. The tectal marginal zone (TMZ) and the ciliary marginal zone (CMZ) are serially homologous structures

Schematic lateral views (A–C) and cross sections (D–I) of zebrafish embryos; yellow shading marks expression of proliferation genes (e.g., impdh2; [45]). These genes are first expressed in the entire alar part of the forebrain/midbrain, but then expression retreats to the stem cell zones of the tectal marginal zone (TMZ) and the ciliary marginal zone (CMZ). (A,D,G) At the 3-somite stage, expression of proliferation genes is in the dorsal part of the anterior neural tube. (B,E,H) At the 15-somite stage, the primordia of the tectum and retina become separated. The retina evaginates, forming the eye cup. Expression of proliferation genes becomes confined to the dorsal eye cup. Complex morphogenetic movements change spatial relationships within the midbrain. Here, proliferation genes retreat towards the mid-dorsal and the ventral part of the alar plate, which invaginates to form the torus semicircularis. (C,F,I) At the 25-somite stage, expression of proliferation genes become restricted to the TMZ and CMZ. The CMZ forms a transitional domain between the neural retina and pigmented epithelium, encircling the lens. Similarly, the TMZ forms a narrow, hinge-like region encircling the lateral and posterior tectum.

Figure 4. Conveyor belt neurogenesis in the visual system of vertebrates and Drosophila

(A,B) Magnified view of schematic sections of the ciliary marginal zone (A; redrawn from [64]) and tectum marginal zone (B; redrawn from [45]). Both CMZ and TMZ can be further subdivided, which is indicated by color coding. At their peripheral edge, the TMZ and CMZ contain stem cells (yellow). Away from this edge one finds the intermediate TMZ (TMZi) and intermediate CMZ (CMZi), both of which have fast amplifying progenitors (light green). Dark green indicates neural precursors exiting the cell cycle. In dark blue are differentiated neurons. (C) Magnified view of schematic section of Drosophila outer optic anlage, generating medulla neurons in a conveyor belt mechanism (for spatial orientation, see Figure 5E). Stippling indicates neuropil. (D) Simplified depiction of neurulation, illustrating inverse apico-basal axis of neuroepithelium in vertebrates and Drosophila. In vertebrates, after invagination of neural tube (bottom panel), apical surface of neuroepithelium containing neural progenitors (yellow) faces inward (ventricular lumen). Postmitotic neurons (blue) and neuropil (stippled) accrete at outer (=basal) surface of neural tube. In Drosophila, optic lobe neuroepithelium, following invagination, does not form a lumen, and apical surface points outward.

Figure 5. Development of the visual system in insects

(A) Microphotograph showing frontal view of embryonic head of the crustacean Hyas araneus (from [54], with permission). An integrated growth zone (PZ1/2; blue label demarcates proliferating cells) generates the eye and outer optic lobe (lamina, medulla), following a temporal gradient. Early born cells (‘e’) are located posteriorly, late born cells (‘l’) anteriorly. (B,C) Schematic lateral views of Drosophila early larva (B) and late larva (C), showing growth zones in eye imaginal disc and optic lobe. (D,E) Schematic section of optic lobe of early larva (D) and late larva (E; based on [,–62]). In (B–E), epithelial optic anlagen and eye disc (giving rise to retina) rendered in yellow; neuroblasts forming from anlagen in light green, neural progeny dark green. Optic anlagen of the early larva are formed by symmetrically dividing neuroepithelia (B,D). In late larva, epithelia convert directionally into asymmetrically, rapidly dividing neuroblasts (E; arrow ‘a’ in inset indicates directionality of epithelium>neuroblast conversion). Neuroblasts produce ganglion mother cells (GMCs)/neurons (arrow ‘b’ in inset to E). The eye disc also undergoes directed growth (arrowheads in C,E). e, early born cells; IOA, inner optic anlage; l, late born cells; OOA, outer optic anlage; OOAl, lateral domain of outer optic anlage; OOAm, medial domain of outer optic anlage.

Figure 6. Conveyor belt neurogenesis in the bilaterian ancestor

Schematic representation of the neuroectoderm of hypothetical primitive bilaterans (top left, bottom center). The inception of the conveyor belt-mode of neurogenesis (top right) in discrete domains of the neurectoderm of the last common ancestor of chordates and arthropods allowed for a more efficient, protracted and temporally coordinated generation of photoreceptors and their target neuropils. The resulting evolution of complex visual systems in the arthropod clades (bottom, left) and chordate clades (bottom, right) greatly enhanced the role of visual input in controlling the locomotion, and thereby the spectrum of visually guided behaviors.