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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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Optix is required for cell survival and adhesion within the neuroepithelium. (A-C”’) Control (FRTG13) and Optix1  mutant MARCM clones were induced in the neuroepithelium (labelled with mCD8-GFP in green). Cells are outlined by Dlg (red), neuroblasts labelled by Dpn (blue). (A-A”’) Wild type clones remain in the neuroepithelium. (B-B”’)Optix1 mutant clones delaminate from the neuroepithelium and show signs of apoptosis, such as cellular fragmentation. (C-C”’)Optix1 mutant clones induced in the lateral neuroepithelium (lateral to the lamina furrow, indicated by yellow arrowhead) do not delaminate or show signs of cell death. Posterior cross-sections are shown in all images. The apico-basal axis of the neuroepithelium is oriented vertically in each image, with the apical surface at the top and the basal surface at the bottom. Scale bars: 30 μm.
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Figure 6: Optix is required for cell survival and adhesion within the neuroepithelium. (A-C”’) Control (FRTG13) and Optix1 mutant MARCM clones were induced in the neuroepithelium (labelled with mCD8-GFP in green). Cells are outlined by Dlg (red), neuroblasts labelled by Dpn (blue). (A-A”’) Wild type clones remain in the neuroepithelium. (B-B”’)Optix1 mutant clones delaminate from the neuroepithelium and show signs of apoptosis, such as cellular fragmentation. (C-C”’)Optix1 mutant clones induced in the lateral neuroepithelium (lateral to the lamina furrow, indicated by yellow arrowhead) do not delaminate or show signs of cell death. Posterior cross-sections are shown in all images. The apico-basal axis of the neuroepithelium is oriented vertically in each image, with the apical surface at the top and the basal surface at the bottom. Scale bars: 30 μm.

Mentions: We analysed the effects of losing Optix function on optic lobe development. Optix mutants are homozygous lethal and die during late embryogenesis [45]. We induced Optix1 mutant MARCM (Mosaic Analysis with a Repressible Cell Marker) clones within the neuroepithelium (Additional file 4; [45,74]). Few mutant clones were recovered in the Optix-expressing region of the neuroepithelium. The Optix mutant clones that could be identified underwent basal extrusion from the neuroepithelium, indicated by their basal cell bodies and elongated apical stalks (Figure 6B, B”). In contrast, control clones or Optix mutant clones induced where Optix is not expressed appeared wild type (Figure 6A-A”’, 6C-C”’). Optix mutant clones showed signs of cell death, including fragmentation, which were not evident in control clones (Figure 6B-B”) They were positively labelled by TUNEL (Terminal deoxynucleotidyl transferase dUTP Nick End Labelling) (Additional file 4) and so we concluded that Optix is required for cell survival in a distinct region of the optic lobe.


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

Gold KS, Brand AH - Neural Dev (2014)

Optix is required for cell survival and adhesion within the neuroepithelium. (A-C”’) Control (FRTG13) and Optix1  mutant MARCM clones were induced in the neuroepithelium (labelled with mCD8-GFP in green). Cells are outlined by Dlg (red), neuroblasts labelled by Dpn (blue). (A-A”’) Wild type clones remain in the neuroepithelium. (B-B”’)Optix1 mutant clones delaminate from the neuroepithelium and show signs of apoptosis, such as cellular fragmentation. (C-C”’)Optix1 mutant clones induced in the lateral neuroepithelium (lateral to the lamina furrow, indicated by yellow arrowhead) do not delaminate or show signs of cell death. Posterior cross-sections are shown in all images. The apico-basal axis of the neuroepithelium is oriented vertically in each image, with the apical surface at the top and the basal surface at the bottom. Scale bars: 30 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Optix is required for cell survival and adhesion within the neuroepithelium. (A-C”’) Control (FRTG13) and Optix1 mutant MARCM clones were induced in the neuroepithelium (labelled with mCD8-GFP in green). Cells are outlined by Dlg (red), neuroblasts labelled by Dpn (blue). (A-A”’) Wild type clones remain in the neuroepithelium. (B-B”’)Optix1 mutant clones delaminate from the neuroepithelium and show signs of apoptosis, such as cellular fragmentation. (C-C”’)Optix1 mutant clones induced in the lateral neuroepithelium (lateral to the lamina furrow, indicated by yellow arrowhead) do not delaminate or show signs of cell death. Posterior cross-sections are shown in all images. The apico-basal axis of the neuroepithelium is oriented vertically in each image, with the apical surface at the top and the basal surface at the bottom. Scale bars: 30 μm.
Mentions: We analysed the effects of losing Optix function on optic lobe development. Optix mutants are homozygous lethal and die during late embryogenesis [45]. We induced Optix1 mutant MARCM (Mosaic Analysis with a Repressible Cell Marker) clones within the neuroepithelium (Additional file 4; [45,74]). Few mutant clones were recovered in the Optix-expressing region of the neuroepithelium. The Optix mutant clones that could be identified underwent basal extrusion from the neuroepithelium, indicated by their basal cell bodies and elongated apical stalks (Figure 6B, B”). In contrast, control clones or Optix mutant clones induced where Optix is not expressed appeared wild type (Figure 6A-A”’, 6C-C”’). Optix mutant clones showed signs of cell death, including fragmentation, which were not evident in control clones (Figure 6B-B”) They were positively labelled by TUNEL (Terminal deoxynucleotidyl transferase dUTP Nick End Labelling) (Additional file 4) and so we concluded that Optix is required for cell survival in a distinct region of the optic lobe.

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