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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

Model for regional neuroepithelial compartments in the optic lobe. (A) Lateral view of the outer proliferation centre (OPC) neuroepithelium (orange), which generates both medulla neuroblasts (green) and lamina precursor cells (grey). (B) The same lateral view of the neuroepithelium, colour coded by the regionalised expression of transcription factors and signalling pathways. Vsx1 (red) is expressed in a central neuroepithelial domain; Optix (green) is expressed in a symmetrical domain on either side. Wingless signalling is active at the tips of the OPC, and activates the Dpp pathway in turn [48].
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Figure 9: Model for regional neuroepithelial compartments in the optic lobe. (A) Lateral view of the outer proliferation centre (OPC) neuroepithelium (orange), which generates both medulla neuroblasts (green) and lamina precursor cells (grey). (B) The same lateral view of the neuroepithelium, colour coded by the regionalised expression of transcription factors and signalling pathways. Vsx1 (red) is expressed in a central neuroepithelial domain; Optix (green) is expressed in a symmetrical domain on either side. Wingless signalling is active at the tips of the OPC, and activates the Dpp pathway in turn [48].

Mentions: The sharply delineated boundaries of Optix expression in the neuroepithelium, and of the lineages derived from this region, suggest that the OPC is compartmentalised. Compartments are classically defined as lineage-restricted populations of cells that do not mix and which may be specified by the expression of a transcription factor or selector gene (reviewed in [53-55,57,58]). We propose that neural stem cells in the OPC have distinct regional identities conferred by the expression of specific transcription factors (Figure 9). This is supported by the reciprocal expression patterns of Optix and Vsx1, and the fact that that Optix misexpression represses Vsx1 expression, raising the possibility that these transcription factors act as selector genes for distinct neuroepithelial regions. Early Optix and Vsx1 expression in the optic lobe could specify ‘founder populations’ of neuroepithelial cells (Figure 3C), which expand through rounds of symmetric division and ultimately establish the proportions of different OPC regions. The posterior Optix expression boundary is reciprocal to the Wingless signalling domain at the tip of the neuroepithelium. The highly regionalised signalling activity of the Wingless and Dpp pathways also contributes to OPC patterning (Figure 9; [48]).


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

Gold KS, Brand AH - Neural Dev (2014)

Model for regional neuroepithelial compartments in the optic lobe. (A) Lateral view of the outer proliferation centre (OPC) neuroepithelium (orange), which generates both medulla neuroblasts (green) and lamina precursor cells (grey). (B) The same lateral view of the neuroepithelium, colour coded by the regionalised expression of transcription factors and signalling pathways. Vsx1 (red) is expressed in a central neuroepithelial domain; Optix (green) is expressed in a symmetrical domain on either side. Wingless signalling is active at the tips of the OPC, and activates the Dpp pathway in turn [48].
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 9: Model for regional neuroepithelial compartments in the optic lobe. (A) Lateral view of the outer proliferation centre (OPC) neuroepithelium (orange), which generates both medulla neuroblasts (green) and lamina precursor cells (grey). (B) The same lateral view of the neuroepithelium, colour coded by the regionalised expression of transcription factors and signalling pathways. Vsx1 (red) is expressed in a central neuroepithelial domain; Optix (green) is expressed in a symmetrical domain on either side. Wingless signalling is active at the tips of the OPC, and activates the Dpp pathway in turn [48].
Mentions: The sharply delineated boundaries of Optix expression in the neuroepithelium, and of the lineages derived from this region, suggest that the OPC is compartmentalised. Compartments are classically defined as lineage-restricted populations of cells that do not mix and which may be specified by the expression of a transcription factor or selector gene (reviewed in [53-55,57,58]). We propose that neural stem cells in the OPC have distinct regional identities conferred by the expression of specific transcription factors (Figure 9). This is supported by the reciprocal expression patterns of Optix and Vsx1, and the fact that that Optix misexpression represses Vsx1 expression, raising the possibility that these transcription factors act as selector genes for distinct neuroepithelial regions. Early Optix and Vsx1 expression in the optic lobe could specify ‘founder populations’ of neuroepithelial cells (Figure 3C), which expand through rounds of symmetric division and ultimately establish the proportions of different OPC regions. The posterior Optix expression boundary is reciprocal to the Wingless signalling domain at the tip of the neuroepithelium. The highly regionalised signalling activity of the Wingless and Dpp pathways also contributes to OPC patterning (Figure 9; [48]).

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