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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 represses Vsx1 expression. (A-B”) Anterior views of late third instar larval brains. Optix misexpression in the VsxGAL4 neuroepithelial domain represses Vsx1 expression. Cells outlined by Dlg (blue), Optix protein in green, Vsx1 in red. (B”) Vsx1 expression is observed in neurons (orange star) but not in neuroepithelial precursors (yellow arrowhead).
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Figure 5: Optix represses Vsx1 expression. (A-B”) Anterior views of late third instar larval brains. Optix misexpression in the VsxGAL4 neuroepithelial domain represses Vsx1 expression. Cells outlined by Dlg (blue), Optix protein in green, Vsx1 in red. (B”) Vsx1 expression is observed in neurons (orange star) but not in neuroepithelial precursors (yellow arrowhead).

Mentions: Optix and Vsx1 proteins are expressed in complementary domains throughout optic lobe development, suggesting that they may be mutually exclusive (Figure 3C-D). Therefore, we tested the consequences of Optix misexpression on the Vsx1 domain (Figure 5A-B”). Optix was ectopically expressed in central Vsx1-expressing neuroepithelial cells using VsxGAL4[62]. This had two clear effects. Firstly, Vsx1 expression was lost from its central neuroepithelial domain (Figure 5B”). The only Vsx1-expressing cells observed in the optic lobe were not neuroepithelial, conforming instead to the wedge-shaped distribution of Vsx1-positive medulla neurons (orange star in Figure 5B”; [62]). Secondly, the morphology of the optic lobe neuroepithelium was distorted compared to wild type brains (Figure 5B’). These results show that ectopic Optix expression in the central neuroepithelial domain disrupts optic lobe patterning. Furthermore, they demonstrate that Optix is sufficient to repress Vsx1 expression, implying potential negative cross-regulation between Optix and Vsx1. This interaction could contribute to the sharp boundaries of Optix and Vsx1 expression in the anterior OPC neuroepithelium. However we did not observe ectopic Vsx1-positive cells in the Optix neuroepithelial compartment upon loss of Optix expression, either in RNAi knockdown conditions or mutant clones (data not shown). This suggests that loss of Optix is not sufficient to induce Vsx1 expression within the Optix domain.


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

Gold KS, Brand AH - Neural Dev (2014)

Optix represses Vsx1 expression. (A-B”) Anterior views of late third instar larval brains. Optix misexpression in the VsxGAL4 neuroepithelial domain represses Vsx1 expression. Cells outlined by Dlg (blue), Optix protein in green, Vsx1 in red. (B”) Vsx1 expression is observed in neurons (orange star) but not in neuroepithelial precursors (yellow arrowhead).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: Optix represses Vsx1 expression. (A-B”) Anterior views of late third instar larval brains. Optix misexpression in the VsxGAL4 neuroepithelial domain represses Vsx1 expression. Cells outlined by Dlg (blue), Optix protein in green, Vsx1 in red. (B”) Vsx1 expression is observed in neurons (orange star) but not in neuroepithelial precursors (yellow arrowhead).
Mentions: Optix and Vsx1 proteins are expressed in complementary domains throughout optic lobe development, suggesting that they may be mutually exclusive (Figure 3C-D). Therefore, we tested the consequences of Optix misexpression on the Vsx1 domain (Figure 5A-B”). Optix was ectopically expressed in central Vsx1-expressing neuroepithelial cells using VsxGAL4[62]. This had two clear effects. Firstly, Vsx1 expression was lost from its central neuroepithelial domain (Figure 5B”). The only Vsx1-expressing cells observed in the optic lobe were not neuroepithelial, conforming instead to the wedge-shaped distribution of Vsx1-positive medulla neurons (orange star in Figure 5B”; [62]). Secondly, the morphology of the optic lobe neuroepithelium was distorted compared to wild type brains (Figure 5B’). These results show that ectopic Optix expression in the central neuroepithelial domain disrupts optic lobe patterning. Furthermore, they demonstrate that Optix is sufficient to repress Vsx1 expression, implying potential negative cross-regulation between Optix and Vsx1. This interaction could contribute to the sharp boundaries of Optix and Vsx1 expression in the anterior OPC neuroepithelium. However we did not observe ectopic Vsx1-positive cells in the Optix neuroepithelial compartment upon loss of Optix expression, either in RNAi knockdown conditions or mutant clones (data not shown). This suggests that loss of Optix is not sufficient to induce Vsx1 expression within the Optix domain.

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