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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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The Acj6-positive cell cluster ventral to the AL is the LALv1 lineage and when  for otd, innervates the AL.(A–D) document a WT MARCM clone of the LALv1 lineage labelled with Per-Gal4. This brain has been immunolabelled with Acj6 (B) and Otd (C). In B, only three clusters of Acj6 positive cells (yellow dotted lines) are seen around each of the ALs (yellow dotted lines). The clusters that are ventral to AL (cyan arrowhead) belong to the LALv1 lineage as seen by the WT MARCM clone shown in A. As expected, these cells are also Otd positive (cyan arrowhead in C). (E–H) show an otd−/− LALv1 MARCM clone. This brain is also immunolabelled with Acj6 (F) and Otd (G). Note that the otd−/− LALv1 cells, which have a transformed neuroanatomy (cyan arrowhead in E), are  for otd (cyan arrowhead in G) but are identifiable as the ventral cluster of Acj6 positive cells (cyan arrowhead in F). Genotype in A–D: FRT19A/FRT19A,Tub-Gal80,hsFLP; Per-Gal4,UAS-mCD8::GFP/+. Genotype in E–H: FRT19A, otdYH13/FRT19A,Tub-Gal80,hsFLP; GH146-Gal4,UAS-mCD8::GFP/+. Scale bar is 50 µm.DOI:http://dx.doi.org/10.7554/eLife.04407.012
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fig7: The Acj6-positive cell cluster ventral to the AL is the LALv1 lineage and when for otd, innervates the AL.(A–D) document a WT MARCM clone of the LALv1 lineage labelled with Per-Gal4. This brain has been immunolabelled with Acj6 (B) and Otd (C). In B, only three clusters of Acj6 positive cells (yellow dotted lines) are seen around each of the ALs (yellow dotted lines). The clusters that are ventral to AL (cyan arrowhead) belong to the LALv1 lineage as seen by the WT MARCM clone shown in A. As expected, these cells are also Otd positive (cyan arrowhead in C). (E–H) show an otd−/− LALv1 MARCM clone. This brain is also immunolabelled with Acj6 (F) and Otd (G). Note that the otd−/− LALv1 cells, which have a transformed neuroanatomy (cyan arrowhead in E), are for otd (cyan arrowhead in G) but are identifiable as the ventral cluster of Acj6 positive cells (cyan arrowhead in F). Genotype in A–D: FRT19A/FRT19A,Tub-Gal80,hsFLP; Per-Gal4,UAS-mCD8::GFP/+. Genotype in E–H: FRT19A, otdYH13/FRT19A,Tub-Gal80,hsFLP; GH146-Gal4,UAS-mCD8::GFP/+. Scale bar is 50 µm.DOI:http://dx.doi.org/10.7554/eLife.04407.012

Mentions: To investigate the identity of the mutant LALv1 lineage further, we identified Acj6 as a molecular marker that could unambiguously identify the LALv1 lineage in wild-type and otd mutants. Acj6 is a POU transcription factor that is known to be expressed in the ALad1 lineage and in a subset of the ALl1-derived projection interneurons of the wild-type brain (Figure 7B). In addition to these two cell clusters, we observed a third Acj6 positive cell cluster ventral to the antennal lobe of the wild-type brain (cyan arrowhead in Figure 7B). MARCM clonal labelling using the Per-Gal4 enhancer line together with anti-Acj6 and anti-Otd antibodies unambiguously identified this cluster as the LALv1 lineage (cyan arrowhead in Figure 7A–D). Importantly, this cell cluster continues to express Acj6 immunoreactivity following mutational inactivation of otd in the LALv1 lineage (Figure 7F,G). Thus, Acj6 provides a molecular marker for the identification of the LALv1 lineage independent of Otd expression in wild-type and mutant clones. The analysis of otd−/− LALv1 MARCM clones identified by Acj6 immunolabelling and co-labelled by GH146-Gal4 shows that the fourth GH146-positive neuroblast clone described above does indeed correspond to the mutant LALv1 lineage (Figure 7E,H). This confirms that upon the loss of otd from the neuroblast, the neural progeny of the LALv1 lineage transform into an antennal lobe fate.10.7554/eLife.04407.012Figure 7.The Acj6-positive cell cluster ventral to the AL is the LALv1 lineage and when for otd, innervates the AL.


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)

The Acj6-positive cell cluster ventral to the AL is the LALv1 lineage and when  for otd, innervates the AL.(A–D) document a WT MARCM clone of the LALv1 lineage labelled with Per-Gal4. This brain has been immunolabelled with Acj6 (B) and Otd (C). In B, only three clusters of Acj6 positive cells (yellow dotted lines) are seen around each of the ALs (yellow dotted lines). The clusters that are ventral to AL (cyan arrowhead) belong to the LALv1 lineage as seen by the WT MARCM clone shown in A. As expected, these cells are also Otd positive (cyan arrowhead in C). (E–H) show an otd−/− LALv1 MARCM clone. This brain is also immunolabelled with Acj6 (F) and Otd (G). Note that the otd−/− LALv1 cells, which have a transformed neuroanatomy (cyan arrowhead in E), are  for otd (cyan arrowhead in G) but are identifiable as the ventral cluster of Acj6 positive cells (cyan arrowhead in F). Genotype in A–D: FRT19A/FRT19A,Tub-Gal80,hsFLP; Per-Gal4,UAS-mCD8::GFP/+. Genotype in E–H: FRT19A, otdYH13/FRT19A,Tub-Gal80,hsFLP; GH146-Gal4,UAS-mCD8::GFP/+. Scale bar is 50 µm.DOI:http://dx.doi.org/10.7554/eLife.04407.012
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4307181&req=5

fig7: The Acj6-positive cell cluster ventral to the AL is the LALv1 lineage and when for otd, innervates the AL.(A–D) document a WT MARCM clone of the LALv1 lineage labelled with Per-Gal4. This brain has been immunolabelled with Acj6 (B) and Otd (C). In B, only three clusters of Acj6 positive cells (yellow dotted lines) are seen around each of the ALs (yellow dotted lines). The clusters that are ventral to AL (cyan arrowhead) belong to the LALv1 lineage as seen by the WT MARCM clone shown in A. As expected, these cells are also Otd positive (cyan arrowhead in C). (E–H) show an otd−/− LALv1 MARCM clone. This brain is also immunolabelled with Acj6 (F) and Otd (G). Note that the otd−/− LALv1 cells, which have a transformed neuroanatomy (cyan arrowhead in E), are for otd (cyan arrowhead in G) but are identifiable as the ventral cluster of Acj6 positive cells (cyan arrowhead in F). Genotype in A–D: FRT19A/FRT19A,Tub-Gal80,hsFLP; Per-Gal4,UAS-mCD8::GFP/+. Genotype in E–H: FRT19A, otdYH13/FRT19A,Tub-Gal80,hsFLP; GH146-Gal4,UAS-mCD8::GFP/+. Scale bar is 50 µm.DOI:http://dx.doi.org/10.7554/eLife.04407.012
Mentions: To investigate the identity of the mutant LALv1 lineage further, we identified Acj6 as a molecular marker that could unambiguously identify the LALv1 lineage in wild-type and otd mutants. Acj6 is a POU transcription factor that is known to be expressed in the ALad1 lineage and in a subset of the ALl1-derived projection interneurons of the wild-type brain (Figure 7B). In addition to these two cell clusters, we observed a third Acj6 positive cell cluster ventral to the antennal lobe of the wild-type brain (cyan arrowhead in Figure 7B). MARCM clonal labelling using the Per-Gal4 enhancer line together with anti-Acj6 and anti-Otd antibodies unambiguously identified this cluster as the LALv1 lineage (cyan arrowhead in Figure 7A–D). Importantly, this cell cluster continues to express Acj6 immunoreactivity following mutational inactivation of otd in the LALv1 lineage (Figure 7F,G). Thus, Acj6 provides a molecular marker for the identification of the LALv1 lineage independent of Otd expression in wild-type and mutant clones. The analysis of otd−/− LALv1 MARCM clones identified by Acj6 immunolabelling and co-labelled by GH146-Gal4 shows that the fourth GH146-positive neuroblast clone described above does indeed correspond to the mutant LALv1 lineage (Figure 7E,H). This confirms that upon the loss of otd from the neuroblast, the neural progeny of the LALv1 lineage transform into an antennal lobe fate.10.7554/eLife.04407.012Figure 7.The Acj6-positive cell cluster ventral to the AL is the LALv1 lineage and when for otd, innervates the AL.

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