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Genetic transformation of structural and functional circuitry rewires the Drosophila brain.

Sen S, Cao D, Choudhary R, Biagini S, Wang JW, Reichert H, VijayRaghavan K - Elife (2014)

Bottom Line: However, the extent to which individual factors can contribute to this is poorly understood.Loss of orthodenticle from this neuroblast affects molecular properties, neuroanatomical features, and functional inputs of progeny neurons, such that an entire central complex lineage transforms into a functional olfactory projection neuron lineage.This ability to change functional macrocircuitry of the brain through changes in gene expression in a single neuroblast reveals a surprising capacity for novel circuit formation in the brain and provides a paradigm for large-scale evolutionary modification of circuitry.

View Article: PubMed Central - PubMed

Affiliation: Department of Developmental Biology and Genetics, National Centre for Biological Sciences, Tata Institute for Fundamental Research, Bangalore, India.

ABSTRACT
Acquisition of distinct neuronal identities during development is critical for the assembly of diverse functional neural circuits in the brain. In both vertebrates and invertebrates, intrinsic determinants are thought to act in neural progenitors to specify their identity and the identity of their neuronal progeny. However, the extent to which individual factors can contribute to this is poorly understood. We investigate the role of orthodenticle in the specification of an identified neuroblast (neuronal progenitor) lineage in the Drosophila brain. Loss of orthodenticle from this neuroblast affects molecular properties, neuroanatomical features, and functional inputs of progeny neurons, such that an entire central complex lineage transforms into a functional olfactory projection neuron lineage. This ability to change functional macrocircuitry of the brain through changes in gene expression in a single neuroblast reveals a surprising capacity for novel circuit formation in the brain and provides a paradigm for large-scale evolutionary modification of circuitry.

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Loss of otd from the LALv1 lineage results in the absence of the LEp tract.(A–D) and (A′–D′) document a brain with a single MARCM labelled otd−/− LALv1 lineage. (A–D) show more posterior sections that contain the tracts of the LALv1 lineage; (A′–D′) show more anterior sections of the same brain that documents its cell bodies. The right brain hemisphere contains an otd−/− LALv1 lineage as seen by the loss of Otd immunolabelling ventral to the antennal lobe (yellow dotted lines in B′), while the left hemisphere contains a wild-type LALv1 lineage (hence not labelled by MARCM) as seen by the presence of Otd immunolabelling (magenta dotted lines in B′). In the left brain hemisphere, which contains the wild-type LALv1 lineage, the loVM (cyan arrow on the left in C) and the LALv1 specific LEp tracts (cyan arrowhead on the left in C) that are identifiable by Neuroglian immunolabelling (highlighted in magenta). In the right brain hemisphere, which contains the otd−/− LALv1 lineage, the loVM tract (taken by other lineages) is still present (cyan arrow on the right in C). The LALv1 specific LEp tract (cyan arrowhead on the right in C) that is exclusively made by the LALv1 lineage, is entirely missing in the right brain hemisphere, which contains the otd−/− LALv1 lineage (cyan arrow on the right in C). The yellow arrowheads in A, C, D point to the new tract of the otd−/− LALv1 lineage innervating the antennal lobe (magenta asterisk). Genotype: FRT19A, otdYH13/FRT19A,Tub-Gal80,hsFLP; GH146-Gal4,UAS-mCD8::GFP/+. The midline is represented by a yellow line in all images.DOI:http://dx.doi.org/10.7554/eLife.04407.011
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fig6: Loss of otd from the LALv1 lineage results in the absence of the LEp tract.(A–D) and (A′–D′) document a brain with a single MARCM labelled otd−/− LALv1 lineage. (A–D) show more posterior sections that contain the tracts of the LALv1 lineage; (A′–D′) show more anterior sections of the same brain that documents its cell bodies. The right brain hemisphere contains an otd−/− LALv1 lineage as seen by the loss of Otd immunolabelling ventral to the antennal lobe (yellow dotted lines in B′), while the left hemisphere contains a wild-type LALv1 lineage (hence not labelled by MARCM) as seen by the presence of Otd immunolabelling (magenta dotted lines in B′). In the left brain hemisphere, which contains the wild-type LALv1 lineage, the loVM (cyan arrow on the left in C) and the LALv1 specific LEp tracts (cyan arrowhead on the left in C) that are identifiable by Neuroglian immunolabelling (highlighted in magenta). In the right brain hemisphere, which contains the otd−/− LALv1 lineage, the loVM tract (taken by other lineages) is still present (cyan arrow on the right in C). The LALv1 specific LEp tract (cyan arrowhead on the right in C) that is exclusively made by the LALv1 lineage, is entirely missing in the right brain hemisphere, which contains the otd−/− LALv1 lineage (cyan arrow on the right in C). The yellow arrowheads in A, C, D point to the new tract of the otd−/− LALv1 lineage innervating the antennal lobe (magenta asterisk). Genotype: FRT19A, otdYH13/FRT19A,Tub-Gal80,hsFLP; GH146-Gal4,UAS-mCD8::GFP/+. The midline is represented by a yellow line in all images.DOI:http://dx.doi.org/10.7554/eLife.04407.011

Mentions: If the loss of otd from the neuroblast of the LALv1 lineage does indeed result in its neuroanatomical transformation into a lineage of a different fate, then this should correspond to the loss of the LALv1-specific axon tract (LEp) in the brain. To investigate this, we first characterized the axon tract of the wild-type LALv1 lineage, which is readily identifiable in the adult brain based on Neuroglian immunolabelling patterns (Pereanu et al., 2010). In wild-type brains, Neuroglian immunolabelling shows the loVM tract (cyan arrow, left hemisphere in Figure 6C,D) and the characteristic LEp tract of the LALv1 lineage, which projects around the antennal lobes and towards the central complex (cyan arrowhead, left hemisphere in Figure 6C,D). In brains in which one LALv1 neuroblast clone is mutant, the brain hemisphere that contains the otd−/− LALv1 neuroblast clone (identified by the loss of Otd immunolabelling; yellow dotted lines in Figure 6B′), still shows the loVM tract (cyan arrow, right hemisphere in Figure 6C,D), which is shared by other lineages. However, the LALv1-specific LEp tract, which projects towards the central complex is entirely missing (cyan arrowhead, right hemisphere in Figure 6C,D). This shows that loss of otd from the LALv1 neuroblast corresponds to the loss of the LEp tract of the wild-type LALv1 lineage, providing support that loss of otd from the LALv1 neuroblast transforms it into a lineage of different identity.10.7554/eLife.04407.011Figure 6.Loss of otd from the LALv1 lineage results in the absence of the LEp tract.


Genetic transformation of structural and functional circuitry rewires the Drosophila brain.

Sen S, Cao D, Choudhary R, Biagini S, Wang JW, Reichert H, VijayRaghavan K - Elife (2014)

Loss of otd from the LALv1 lineage results in the absence of the LEp tract.(A–D) and (A′–D′) document a brain with a single MARCM labelled otd−/− LALv1 lineage. (A–D) show more posterior sections that contain the tracts of the LALv1 lineage; (A′–D′) show more anterior sections of the same brain that documents its cell bodies. The right brain hemisphere contains an otd−/− LALv1 lineage as seen by the loss of Otd immunolabelling ventral to the antennal lobe (yellow dotted lines in B′), while the left hemisphere contains a wild-type LALv1 lineage (hence not labelled by MARCM) as seen by the presence of Otd immunolabelling (magenta dotted lines in B′). In the left brain hemisphere, which contains the wild-type LALv1 lineage, the loVM (cyan arrow on the left in C) and the LALv1 specific LEp tracts (cyan arrowhead on the left in C) that are identifiable by Neuroglian immunolabelling (highlighted in magenta). In the right brain hemisphere, which contains the otd−/− LALv1 lineage, the loVM tract (taken by other lineages) is still present (cyan arrow on the right in C). The LALv1 specific LEp tract (cyan arrowhead on the right in C) that is exclusively made by the LALv1 lineage, is entirely missing in the right brain hemisphere, which contains the otd−/− LALv1 lineage (cyan arrow on the right in C). The yellow arrowheads in A, C, D point to the new tract of the otd−/− LALv1 lineage innervating the antennal lobe (magenta asterisk). Genotype: FRT19A, otdYH13/FRT19A,Tub-Gal80,hsFLP; GH146-Gal4,UAS-mCD8::GFP/+. The midline is represented by a yellow line in all images.DOI:http://dx.doi.org/10.7554/eLife.04407.011
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fig6: Loss of otd from the LALv1 lineage results in the absence of the LEp tract.(A–D) and (A′–D′) document a brain with a single MARCM labelled otd−/− LALv1 lineage. (A–D) show more posterior sections that contain the tracts of the LALv1 lineage; (A′–D′) show more anterior sections of the same brain that documents its cell bodies. The right brain hemisphere contains an otd−/− LALv1 lineage as seen by the loss of Otd immunolabelling ventral to the antennal lobe (yellow dotted lines in B′), while the left hemisphere contains a wild-type LALv1 lineage (hence not labelled by MARCM) as seen by the presence of Otd immunolabelling (magenta dotted lines in B′). In the left brain hemisphere, which contains the wild-type LALv1 lineage, the loVM (cyan arrow on the left in C) and the LALv1 specific LEp tracts (cyan arrowhead on the left in C) that are identifiable by Neuroglian immunolabelling (highlighted in magenta). In the right brain hemisphere, which contains the otd−/− LALv1 lineage, the loVM tract (taken by other lineages) is still present (cyan arrow on the right in C). The LALv1 specific LEp tract (cyan arrowhead on the right in C) that is exclusively made by the LALv1 lineage, is entirely missing in the right brain hemisphere, which contains the otd−/− LALv1 lineage (cyan arrow on the right in C). The yellow arrowheads in A, C, D point to the new tract of the otd−/− LALv1 lineage innervating the antennal lobe (magenta asterisk). Genotype: FRT19A, otdYH13/FRT19A,Tub-Gal80,hsFLP; GH146-Gal4,UAS-mCD8::GFP/+. The midline is represented by a yellow line in all images.DOI:http://dx.doi.org/10.7554/eLife.04407.011
Mentions: If the loss of otd from the neuroblast of the LALv1 lineage does indeed result in its neuroanatomical transformation into a lineage of a different fate, then this should correspond to the loss of the LALv1-specific axon tract (LEp) in the brain. To investigate this, we first characterized the axon tract of the wild-type LALv1 lineage, which is readily identifiable in the adult brain based on Neuroglian immunolabelling patterns (Pereanu et al., 2010). In wild-type brains, Neuroglian immunolabelling shows the loVM tract (cyan arrow, left hemisphere in Figure 6C,D) and the characteristic LEp tract of the LALv1 lineage, which projects around the antennal lobes and towards the central complex (cyan arrowhead, left hemisphere in Figure 6C,D). In brains in which one LALv1 neuroblast clone is mutant, the brain hemisphere that contains the otd−/− LALv1 neuroblast clone (identified by the loss of Otd immunolabelling; yellow dotted lines in Figure 6B′), still shows the loVM tract (cyan arrow, right hemisphere in Figure 6C,D), which is shared by other lineages. However, the LALv1-specific LEp tract, which projects towards the central complex is entirely missing (cyan arrowhead, right hemisphere in Figure 6C,D). This shows that loss of otd from the LALv1 neuroblast corresponds to the loss of the LEp tract of the wild-type LALv1 lineage, providing support that loss of otd from the LALv1 neuroblast transforms it into a lineage of different identity.10.7554/eLife.04407.011Figure 6.Loss of otd from the LALv1 lineage results in the absence of the LEp tract.

Bottom Line: However, the extent to which individual factors can contribute to this is poorly understood.Loss of orthodenticle from this neuroblast affects molecular properties, neuroanatomical features, and functional inputs of progeny neurons, such that an entire central complex lineage transforms into a functional olfactory projection neuron lineage.This ability to change functional macrocircuitry of the brain through changes in gene expression in a single neuroblast reveals a surprising capacity for novel circuit formation in the brain and provides a paradigm for large-scale evolutionary modification of circuitry.

View Article: PubMed Central - PubMed

Affiliation: Department of Developmental Biology and Genetics, National Centre for Biological Sciences, Tata Institute for Fundamental Research, Bangalore, India.

ABSTRACT
Acquisition of distinct neuronal identities during development is critical for the assembly of diverse functional neural circuits in the brain. In both vertebrates and invertebrates, intrinsic determinants are thought to act in neural progenitors to specify their identity and the identity of their neuronal progeny. However, the extent to which individual factors can contribute to this is poorly understood. We investigate the role of orthodenticle in the specification of an identified neuroblast (neuronal progenitor) lineage in the Drosophila brain. Loss of orthodenticle from this neuroblast affects molecular properties, neuroanatomical features, and functional inputs of progeny neurons, such that an entire central complex lineage transforms into a functional olfactory projection neuron lineage. This ability to change functional macrocircuitry of the brain through changes in gene expression in a single neuroblast reveals a surprising capacity for novel circuit formation in the brain and provides a paradigm for large-scale evolutionary modification of circuitry.

Show MeSH
Related in: MedlinePlus