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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 expression defines a restricted neuroepithelial lineage. (A) Anterior view of a late third instar brain lobe. G-TRACE lineage tracing was performed using OptixGAL4. The GFP and RFP-labelled OptixGAL4 lineage forms much of the medulla and part of the lamina neuronal cortices, aside from a clear central gap (yellow star). La, lamina cortex; me, medulla cortex. Lamina neurons are labelled by Dac (blue). (B) Anterior view of a late third instar brain lobe. The outer proliferation centre (OPC) neuroepithelium is outlined by the dashed white line. There is a sharp expression boundary (yellow arrowhead) between the OptixGAL4 lineage derived from Optix-expressing neuroepithelial cells (GFP, green) and Vsx1-expressing neuroepithelial cells (red). (B’) Vsx1 is also expressed in medulla neurons that migrate and intermingle with medulla neurons derived from the OptixGAL4 lineage. (C) Larval brain at 12 hours after larval hatching (ALH). Optix (green) and Vsx1 (red) are expressed in complementary domains. Fas II (blue) labels early neuroepithelial cells. Yellow arrow indicates Vsx1 domain. (D) Anterior view of larval brain at 96 hours ALH. Optix (green) and Vsx1 (red) are expressed in complementary domains. Cells outlined by Dlg (blue). Yellow arrow indicates Vsx1 domain.
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Figure 3: Optix expression defines a restricted neuroepithelial lineage. (A) Anterior view of a late third instar brain lobe. G-TRACE lineage tracing was performed using OptixGAL4. The GFP and RFP-labelled OptixGAL4 lineage forms much of the medulla and part of the lamina neuronal cortices, aside from a clear central gap (yellow star). La, lamina cortex; me, medulla cortex. Lamina neurons are labelled by Dac (blue). (B) Anterior view of a late third instar brain lobe. The outer proliferation centre (OPC) neuroepithelium is outlined by the dashed white line. There is a sharp expression boundary (yellow arrowhead) between the OptixGAL4 lineage derived from Optix-expressing neuroepithelial cells (GFP, green) and Vsx1-expressing neuroepithelial cells (red). (B’) Vsx1 is also expressed in medulla neurons that migrate and intermingle with medulla neurons derived from the OptixGAL4 lineage. (C) Larval brain at 12 hours after larval hatching (ALH). Optix (green) and Vsx1 (red) are expressed in complementary domains. Fas II (blue) labels early neuroepithelial cells. Yellow arrow indicates Vsx1 domain. (D) Anterior view of larval brain at 96 hours ALH. Optix (green) and Vsx1 (red) are expressed in complementary domains. Cells outlined by Dlg (blue). Yellow arrow indicates Vsx1 domain.

Mentions: The medulla and lamina are two of the visual processing ganglia in the adult optic lobe. Medulla and lamina neurons both derive from OPC neuroepithelial cells [34]. Lineage tracing analysis revealed that Optix-expressing neuroepithelial cells give rise to a neural lineage that forms much of the medulla cortex and also part of the lamina (Figure 3A-A’). The boundaries of the cell lineages derived from Optix-positive neuroepithelial cells are straight, with a clear central gap (Figure 3A-A’ , Figure 3B-B’). This gap corresponds to the anterior boundaries of Optix expression (Figure 1D). Interestingly it had previously been reported that the transcription factor Vsx1 is expressed in the central neuroepithelium [62]. Vsx1 is a Drosophila homologue of the homeodomain protein Chx10, which is essential for retinal progenitor cell proliferation and neuronal specification in vertebrates [63]. Vsx1 is expressed in a central population of OPC neuroepithelial cells and a subset of medulla neurons, and is required for neuroepithelial proliferation [62]. We found that Optix and Vsx1 are expressed in complementary neuroepithelial domains throughout optic lobe development (Figure 3B-D”). Vsx1 protein was also observed in medulla neurons, which migrate and mix with neurons derived from the OptixGAL4 lineage. These lineage tracing results, and the complementary expression of Optix and Vsx1, support a model in which the optic lobe neuroepithelium is compartmentalised by transcription factor expression.


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

Gold KS, Brand AH - Neural Dev (2014)

Optix expression defines a restricted neuroepithelial lineage. (A) Anterior view of a late third instar brain lobe. G-TRACE lineage tracing was performed using OptixGAL4. The GFP and RFP-labelled OptixGAL4 lineage forms much of the medulla and part of the lamina neuronal cortices, aside from a clear central gap (yellow star). La, lamina cortex; me, medulla cortex. Lamina neurons are labelled by Dac (blue). (B) Anterior view of a late third instar brain lobe. The outer proliferation centre (OPC) neuroepithelium is outlined by the dashed white line. There is a sharp expression boundary (yellow arrowhead) between the OptixGAL4 lineage derived from Optix-expressing neuroepithelial cells (GFP, green) and Vsx1-expressing neuroepithelial cells (red). (B’) Vsx1 is also expressed in medulla neurons that migrate and intermingle with medulla neurons derived from the OptixGAL4 lineage. (C) Larval brain at 12 hours after larval hatching (ALH). Optix (green) and Vsx1 (red) are expressed in complementary domains. Fas II (blue) labels early neuroepithelial cells. Yellow arrow indicates Vsx1 domain. (D) Anterior view of larval brain at 96 hours ALH. Optix (green) and Vsx1 (red) are expressed in complementary domains. Cells outlined by Dlg (blue). Yellow arrow indicates Vsx1 domain.
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Related In: Results  -  Collection

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Figure 3: Optix expression defines a restricted neuroepithelial lineage. (A) Anterior view of a late third instar brain lobe. G-TRACE lineage tracing was performed using OptixGAL4. The GFP and RFP-labelled OptixGAL4 lineage forms much of the medulla and part of the lamina neuronal cortices, aside from a clear central gap (yellow star). La, lamina cortex; me, medulla cortex. Lamina neurons are labelled by Dac (blue). (B) Anterior view of a late third instar brain lobe. The outer proliferation centre (OPC) neuroepithelium is outlined by the dashed white line. There is a sharp expression boundary (yellow arrowhead) between the OptixGAL4 lineage derived from Optix-expressing neuroepithelial cells (GFP, green) and Vsx1-expressing neuroepithelial cells (red). (B’) Vsx1 is also expressed in medulla neurons that migrate and intermingle with medulla neurons derived from the OptixGAL4 lineage. (C) Larval brain at 12 hours after larval hatching (ALH). Optix (green) and Vsx1 (red) are expressed in complementary domains. Fas II (blue) labels early neuroepithelial cells. Yellow arrow indicates Vsx1 domain. (D) Anterior view of larval brain at 96 hours ALH. Optix (green) and Vsx1 (red) are expressed in complementary domains. Cells outlined by Dlg (blue). Yellow arrow indicates Vsx1 domain.
Mentions: The medulla and lamina are two of the visual processing ganglia in the adult optic lobe. Medulla and lamina neurons both derive from OPC neuroepithelial cells [34]. Lineage tracing analysis revealed that Optix-expressing neuroepithelial cells give rise to a neural lineage that forms much of the medulla cortex and also part of the lamina (Figure 3A-A’). The boundaries of the cell lineages derived from Optix-positive neuroepithelial cells are straight, with a clear central gap (Figure 3A-A’ , Figure 3B-B’). This gap corresponds to the anterior boundaries of Optix expression (Figure 1D). Interestingly it had previously been reported that the transcription factor Vsx1 is expressed in the central neuroepithelium [62]. Vsx1 is a Drosophila homologue of the homeodomain protein Chx10, which is essential for retinal progenitor cell proliferation and neuronal specification in vertebrates [63]. Vsx1 is expressed in a central population of OPC neuroepithelial cells and a subset of medulla neurons, and is required for neuroepithelial proliferation [62]. We found that Optix and Vsx1 are expressed in complementary neuroepithelial domains throughout optic lobe development (Figure 3B-D”). Vsx1 protein was also observed in medulla neurons, which migrate and mix with neurons derived from the OptixGAL4 lineage. These lineage tracing results, and the complementary expression of Optix and Vsx1, support a model in which the optic lobe neuroepithelium is compartmentalised by transcription factor expression.

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