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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 neuroepithelial expression boundaries are maintained during overproliferation. (A) Anterior view of wild type third instar brain lobe shows Optix is expressed in the neuroepithelium with a central gap (indicated by dashed white lines). (B, C) Fat-Hippo signalling disruption in ds05142 mutants induces neuroepithelial overproliferation. Optix expression is still absent from the central domain of the anterior outer proliferation centre (OPC) neuroepithelium (dashed lines), and the boundary between Optix-positive and Optix-negative cells is straight. (A-C) Optix protein is in green, cells are outlined by Dlg staining in red.
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Figure 4: Optix neuroepithelial expression boundaries are maintained during overproliferation. (A) Anterior view of wild type third instar brain lobe shows Optix is expressed in the neuroepithelium with a central gap (indicated by dashed white lines). (B, C) Fat-Hippo signalling disruption in ds05142 mutants induces neuroepithelial overproliferation. Optix expression is still absent from the central domain of the anterior outer proliferation centre (OPC) neuroepithelium (dashed lines), and the boundary between Optix-positive and Optix-negative cells is straight. (A-C) Optix protein is in green, cells are outlined by Dlg staining in red.

Mentions: ds05142 brains are grossly distorted owing to neuroepithelial overproliferation (Figure 4). Despite this, a sharp Optix expression domain is still visible in the optic lobe. This region is larger than in wild type as a consequence of tissue overgrowth, but it still possesses a discrete expression boundary (Figure 4A’ , B’ , C’). The persistence of the anterior expression boundary (which is usually ‘filled in’ by Vsx1 expression) suggests a mechanism is in place to ensure that Optix-expressing cells do not intermingle with their Optix-negative neighbours, even under conditions of extensive overgrowth. This supports our hypothesis that the neuroepithelium is subdivided into compartments defined by transcription factor expression, which are, remarkably, maintained during neoplasia.


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

Gold KS, Brand AH - Neural Dev (2014)

Optix neuroepithelial expression boundaries are maintained during overproliferation. (A) Anterior view of wild type third instar brain lobe shows Optix is expressed in the neuroepithelium with a central gap (indicated by dashed white lines). (B, C) Fat-Hippo signalling disruption in ds05142 mutants induces neuroepithelial overproliferation. Optix expression is still absent from the central domain of the anterior outer proliferation centre (OPC) neuroepithelium (dashed lines), and the boundary between Optix-positive and Optix-negative cells is straight. (A-C) Optix protein is in green, cells are outlined by Dlg staining in red.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Optix neuroepithelial expression boundaries are maintained during overproliferation. (A) Anterior view of wild type third instar brain lobe shows Optix is expressed in the neuroepithelium with a central gap (indicated by dashed white lines). (B, C) Fat-Hippo signalling disruption in ds05142 mutants induces neuroepithelial overproliferation. Optix expression is still absent from the central domain of the anterior outer proliferation centre (OPC) neuroepithelium (dashed lines), and the boundary between Optix-positive and Optix-negative cells is straight. (A-C) Optix protein is in green, cells are outlined by Dlg staining in red.
Mentions: ds05142 brains are grossly distorted owing to neuroepithelial overproliferation (Figure 4). Despite this, a sharp Optix expression domain is still visible in the optic lobe. This region is larger than in wild type as a consequence of tissue overgrowth, but it still possesses a discrete expression boundary (Figure 4A’ , B’ , C’). The persistence of the anterior expression boundary (which is usually ‘filled in’ by Vsx1 expression) suggests a mechanism is in place to ensure that Optix-expressing cells do not intermingle with their Optix-negative neighbours, even under conditions of extensive overgrowth. This supports our hypothesis that the neuroepithelium is subdivided into compartments defined by transcription factor expression, which are, remarkably, maintained during neoplasia.

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