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Optix defines a neuroepithelial compartment in the optic lobe of the Drosophila brain.

Gold KS, Brand AH - Neural Dev (2014)

Bottom Line: Neuroepithelia are regionalised by the expression of transcription factors and signalling molecules, resulting in the formation of distinct developmental, and ultimately functional, domains.Six3 and Six6 are required for mammalian eye and forebrain development, and mutations in humans are associated with severe eye and brain malformation.Our findings provide insight into the spatial patterning of a complex region of the brain, and suggest an evolutionarily conserved principle of visual system development.

View Article: PubMed Central - HTML - PubMed

Affiliation: The Gurdon Institute and Department of Physiology, Development & Neuroscience, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK. a.brand@gurdon.cam.ac.uk.

ABSTRACT

Background: During early brain development, the organisation of neural progenitors into a neuroepithelial sheet maintains tissue integrity during growth. Neuroepithelial cohesion and patterning is essential for orderly proliferation and neural fate specification. Neuroepithelia are regionalised by the expression of transcription factors and signalling molecules, resulting in the formation of distinct developmental, and ultimately functional, domains.

Results: We have discovered that the Six3/6 family orthologue Optix is an essential regulator of neuroepithelial maintenance and patterning in the Drosophila brain. Six3 and Six6 are required for mammalian eye and forebrain development, and mutations in humans are associated with severe eye and brain malformation. In Drosophila, Optix is expressed in a sharply defined region of the larval optic lobe, and its expression is reciprocal to that of the transcription factor Vsx1. Optix gain- and loss-of-function affects neuroepithelial adhesion, integrity and polarity. We find restricted cell lineage boundaries that correspond to transcription factor expression domains.

Conclusion: We propose that the optic lobe is compartmentalised by expression of Optix and Vsx1. Our findings provide insight into the spatial patterning of a complex region of the brain, and suggest an evolutionarily conserved principle of visual system development.

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Related in: MedlinePlus

Optix is expressed in half of the optic lobe neuroepithelium. (A) Cartoon of a lateral view of larval third instar brain lobes. The optic lobe outer proliferation centre (OPC) is a horseshoe-shaped neuroepithelium (orange), which covers the lateral side of each brain lobe. A frontal cross-section is indicated by the dotted square. Dorsal-ventral, anterior-posterior and medial-lateral axes indicated by arrows. (B) Cartoon of a posterior frontal cross-section through a brain lobe at mid third instar. The OPC neuroepithelium (NE) generates two kinds of neural precursor: asymmetrically dividing medulla neuroblasts (NBs, green) and lamina precursor cells (LPCs, grey). Incoming retinal axons in the optic nerve enter through the central gap in the neuroepithelium. Medial-lateral axis indicated by arrows. (C) Cartoon of a lateral view from (A) showing the planes of two frontal cross-sections (dotted squares), one anterior (A) and one posterior (P). (D) Anterior confocal cross-section through a brain lobe at mid third instar. Cells are outlined in red by Discs large (Dlg) staining. Optix protein (green) is expressed across the neuroepithelium with a central gap. (E) Posterior confocal cross-section through a brain lobe at mid third instar. Cells are outlined in red by Actin staining (Phalloidin). Optix protein (green) is symmetrically expressed across the neuroepithelium with a sharp boundary.
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Figure 1: Optix is expressed in half of the optic lobe neuroepithelium. (A) Cartoon of a lateral view of larval third instar brain lobes. The optic lobe outer proliferation centre (OPC) is a horseshoe-shaped neuroepithelium (orange), which covers the lateral side of each brain lobe. A frontal cross-section is indicated by the dotted square. Dorsal-ventral, anterior-posterior and medial-lateral axes indicated by arrows. (B) Cartoon of a posterior frontal cross-section through a brain lobe at mid third instar. The OPC neuroepithelium (NE) generates two kinds of neural precursor: asymmetrically dividing medulla neuroblasts (NBs, green) and lamina precursor cells (LPCs, grey). Incoming retinal axons in the optic nerve enter through the central gap in the neuroepithelium. Medial-lateral axis indicated by arrows. (C) Cartoon of a lateral view from (A) showing the planes of two frontal cross-sections (dotted squares), one anterior (A) and one posterior (P). (D) Anterior confocal cross-section through a brain lobe at mid third instar. Cells are outlined in red by Discs large (Dlg) staining. Optix protein (green) is expressed across the neuroepithelium with a central gap. (E) Posterior confocal cross-section through a brain lobe at mid third instar. Cells are outlined in red by Actin staining (Phalloidin). Optix protein (green) is symmetrically expressed across the neuroepithelium with a sharp boundary.

Mentions: We investigated which genes were expressed in the optic lobe neuroepithelium using transcriptome analysis [21,47]. This led to the identification of Optix, which was significantly upregulated in neuroepithelial cells compared to optic lobe neuroblasts. We analysed Optix protein expression in the optic lobe and found that it is strikingly enriched in the optic lobe outer proliferation centre. The outer proliferation centre (OPC) is a horseshoe-shaped neuroepithelium, which covers the lateral side of each brain lobe (Figure 1A, 1B). Each neuroepithelial arm gives rise to medulla neuroblasts (NBs) at the medial edge and lamina precursor cells (LPCs) at the lateral edge (Figure 1B). Optix is expressed in a symmetric domain in the two halves of the neuroepithelium (Figure 1C-E). It has a central gap in the anterior-most neuroepithelium (Figure 1D) and a particularly sharp posterior boundary of expression (Figure 1E). Interestingly, this posterior expression boundary abuts the Wingless signalling domain at the tips of the posterior OPC arms (Additional file 1; [48]). Optix protein expression is downregulated at the transition zone, where medial neuroepithelial cells become medulla neuroblasts and start dividing asymmetrically (Additional file 1). We noted Optix expression in other cell types in the brain, including glia and central brain neuroblast lineages (Additional file 2; [49]). These results indicated that Optix could potentially regulate brain development, in addition to its previously characterised role in retinal determination.


Optix defines a neuroepithelial compartment in the optic lobe of the Drosophila brain.

Gold KS, Brand AH - Neural Dev (2014)

Optix is expressed in half of the optic lobe neuroepithelium. (A) Cartoon of a lateral view of larval third instar brain lobes. The optic lobe outer proliferation centre (OPC) is a horseshoe-shaped neuroepithelium (orange), which covers the lateral side of each brain lobe. A frontal cross-section is indicated by the dotted square. Dorsal-ventral, anterior-posterior and medial-lateral axes indicated by arrows. (B) Cartoon of a posterior frontal cross-section through a brain lobe at mid third instar. The OPC neuroepithelium (NE) generates two kinds of neural precursor: asymmetrically dividing medulla neuroblasts (NBs, green) and lamina precursor cells (LPCs, grey). Incoming retinal axons in the optic nerve enter through the central gap in the neuroepithelium. Medial-lateral axis indicated by arrows. (C) Cartoon of a lateral view from (A) showing the planes of two frontal cross-sections (dotted squares), one anterior (A) and one posterior (P). (D) Anterior confocal cross-section through a brain lobe at mid third instar. Cells are outlined in red by Discs large (Dlg) staining. Optix protein (green) is expressed across the neuroepithelium with a central gap. (E) Posterior confocal cross-section through a brain lobe at mid third instar. Cells are outlined in red by Actin staining (Phalloidin). Optix protein (green) is symmetrically expressed across the neuroepithelium with a sharp boundary.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4127074&req=5

Figure 1: Optix is expressed in half of the optic lobe neuroepithelium. (A) Cartoon of a lateral view of larval third instar brain lobes. The optic lobe outer proliferation centre (OPC) is a horseshoe-shaped neuroepithelium (orange), which covers the lateral side of each brain lobe. A frontal cross-section is indicated by the dotted square. Dorsal-ventral, anterior-posterior and medial-lateral axes indicated by arrows. (B) Cartoon of a posterior frontal cross-section through a brain lobe at mid third instar. The OPC neuroepithelium (NE) generates two kinds of neural precursor: asymmetrically dividing medulla neuroblasts (NBs, green) and lamina precursor cells (LPCs, grey). Incoming retinal axons in the optic nerve enter through the central gap in the neuroepithelium. Medial-lateral axis indicated by arrows. (C) Cartoon of a lateral view from (A) showing the planes of two frontal cross-sections (dotted squares), one anterior (A) and one posterior (P). (D) Anterior confocal cross-section through a brain lobe at mid third instar. Cells are outlined in red by Discs large (Dlg) staining. Optix protein (green) is expressed across the neuroepithelium with a central gap. (E) Posterior confocal cross-section through a brain lobe at mid third instar. Cells are outlined in red by Actin staining (Phalloidin). Optix protein (green) is symmetrically expressed across the neuroepithelium with a sharp boundary.
Mentions: We investigated which genes were expressed in the optic lobe neuroepithelium using transcriptome analysis [21,47]. This led to the identification of Optix, which was significantly upregulated in neuroepithelial cells compared to optic lobe neuroblasts. We analysed Optix protein expression in the optic lobe and found that it is strikingly enriched in the optic lobe outer proliferation centre. The outer proliferation centre (OPC) is a horseshoe-shaped neuroepithelium, which covers the lateral side of each brain lobe (Figure 1A, 1B). Each neuroepithelial arm gives rise to medulla neuroblasts (NBs) at the medial edge and lamina precursor cells (LPCs) at the lateral edge (Figure 1B). Optix is expressed in a symmetric domain in the two halves of the neuroepithelium (Figure 1C-E). It has a central gap in the anterior-most neuroepithelium (Figure 1D) and a particularly sharp posterior boundary of expression (Figure 1E). Interestingly, this posterior expression boundary abuts the Wingless signalling domain at the tips of the posterior OPC arms (Additional file 1; [48]). Optix protein expression is downregulated at the transition zone, where medial neuroepithelial cells become medulla neuroblasts and start dividing asymmetrically (Additional file 1). We noted Optix expression in other cell types in the brain, including glia and central brain neuroblast lineages (Additional file 2; [49]). These results indicated that Optix could potentially regulate brain development, in addition to its previously characterised role in retinal determination.

Bottom Line: Neuroepithelia are regionalised by the expression of transcription factors and signalling molecules, resulting in the formation of distinct developmental, and ultimately functional, domains.Six3 and Six6 are required for mammalian eye and forebrain development, and mutations in humans are associated with severe eye and brain malformation.Our findings provide insight into the spatial patterning of a complex region of the brain, and suggest an evolutionarily conserved principle of visual system development.

View Article: PubMed Central - HTML - PubMed

Affiliation: The Gurdon Institute and Department of Physiology, Development & Neuroscience, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK. a.brand@gurdon.cam.ac.uk.

ABSTRACT

Background: During early brain development, the organisation of neural progenitors into a neuroepithelial sheet maintains tissue integrity during growth. Neuroepithelial cohesion and patterning is essential for orderly proliferation and neural fate specification. Neuroepithelia are regionalised by the expression of transcription factors and signalling molecules, resulting in the formation of distinct developmental, and ultimately functional, domains.

Results: We have discovered that the Six3/6 family orthologue Optix is an essential regulator of neuroepithelial maintenance and patterning in the Drosophila brain. Six3 and Six6 are required for mammalian eye and forebrain development, and mutations in humans are associated with severe eye and brain malformation. In Drosophila, Optix is expressed in a sharply defined region of the larval optic lobe, and its expression is reciprocal to that of the transcription factor Vsx1. Optix gain- and loss-of-function affects neuroepithelial adhesion, integrity and polarity. We find restricted cell lineage boundaries that correspond to transcription factor expression domains.

Conclusion: We propose that the optic lobe is compartmentalised by expression of Optix and Vsx1. Our findings provide insight into the spatial patterning of a complex region of the brain, and suggest an evolutionarily conserved principle of visual system development.

Show MeSH
Related in: MedlinePlus