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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 an extra, fourth antennal lobe lineage labelled by the GH146 enhancer.(A–C) document a MARCM clonal brain, in which the clones  for otd function and are labelled by the GH146-Gal4. In this brain, the three known antennal lobe lineages normally labelled by GH146-Gal4 (ALad1, ALl1, and Alv1) have been recovered, along with an additional fourth neuroblast lineage, LALv1. (D–G) document a control brain where Otd is not down regulated in the LALv1 lineage (yellow dotted lines in E). In this brain, there are three clusters of antennal lobe projection neurons labelled by GH146-QF corresponding to the ALad1, ALl1 and ALv1 lineages, magenta dotted lines in D and G). (H–K) show a brain in which there has been efficient knock down of Otd in the LALv1 lineage (note loss of Otd immunolabelling ventral to the antennal lobe; yellow dotted lines in I). In this brain, apart from the ALad1, ALl1, and ALv1 projection neurons, an additional, fourth cluster of cells is seen innervating the antennal lobe (‘4’, LALv1). The yellow asterisks in A, D, H indicate the point of entry of the ALv1 lineage into the antennal lobe, and the yellow arrow indicates its axon tract. The magenta asterisks in A, D, H indicate the point of entry of the LALv1 lineage into the antennal lobe, and the magenta arrow indicates its axon tract. Note that these are distinct from each other. Genotype in A–C: FRT19A,otdYH13/FRT19A,Tub-Gal80,hsFLP; GH146-Gal4,UAS-mCD8::GFP/+. Genotype in D–K: UASdicer/+;Insc-Gal4/UAS-miRNA-otd-1;GH146-QF,QUAS-mtdTomato-HA/+). Scale bars are 50 µm. The one in A is applicable to B and C and the one in in D is applicable to D–K. Yellow line represents the midline.DOI:http://dx.doi.org/10.7554/eLife.04407.010
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fig5: Loss of otd from the LALv1 lineage results in an extra, fourth antennal lobe lineage labelled by the GH146 enhancer.(A–C) document a MARCM clonal brain, in which the clones for otd function and are labelled by the GH146-Gal4. In this brain, the three known antennal lobe lineages normally labelled by GH146-Gal4 (ALad1, ALl1, and Alv1) have been recovered, along with an additional fourth neuroblast lineage, LALv1. (D–G) document a control brain where Otd is not down regulated in the LALv1 lineage (yellow dotted lines in E). In this brain, there are three clusters of antennal lobe projection neurons labelled by GH146-QF corresponding to the ALad1, ALl1 and ALv1 lineages, magenta dotted lines in D and G). (H–K) show a brain in which there has been efficient knock down of Otd in the LALv1 lineage (note loss of Otd immunolabelling ventral to the antennal lobe; yellow dotted lines in I). In this brain, apart from the ALad1, ALl1, and ALv1 projection neurons, an additional, fourth cluster of cells is seen innervating the antennal lobe (‘4’, LALv1). The yellow asterisks in A, D, H indicate the point of entry of the ALv1 lineage into the antennal lobe, and the yellow arrow indicates its axon tract. The magenta asterisks in A, D, H indicate the point of entry of the LALv1 lineage into the antennal lobe, and the magenta arrow indicates its axon tract. Note that these are distinct from each other. Genotype in A–C: FRT19A,otdYH13/FRT19A,Tub-Gal80,hsFLP; GH146-Gal4,UAS-mCD8::GFP/+. Genotype in D–K: UASdicer/+;Insc-Gal4/UAS-miRNA-otd-1;GH146-QF,QUAS-mtdTomato-HA/+). Scale bars are 50 µm. The one in A is applicable to B and C and the one in in D is applicable to D–K. Yellow line represents the midline.DOI:http://dx.doi.org/10.7554/eLife.04407.010

Mentions: The cell body position of this type of otd−/− clone as well as the entry point of its tract into the antennal lobe (both ventro-medial) did not correspond to any of the known GH146-Gal4 labelled antennal lobe lineages (Ito et al., 2013; Yu et al., 2013). Importantly, this is also true for the ALv1 lineage, whose cell bodies are also located ventral to the antennal lobe; despite the ventral cell body position of the LALv1 and ALv1 lineages, their overall neuroanatomy is very different from each other. The neurites of the otd−/− LALv1 lineage enter the lobe medially (magenta asterisk in Figure 5A,D,H) while the neurites of the ALv1 (as well as the otd−/− ALv1) enter it laterally (yellow asterisk in Figure 5A,D,H). Moreover, while the otd−/− LALv1 lineage uses the medial antennal lobe tract (magenta arrow in Figure 5A,D,H), the ALv1 (as well as the otd−/− ALv1) uses the mediolateral antennal lobe tract (yellow arrow in Figure 5A,C). Finally, while the otd−/− LALv1 lineage first innervates the calyx of the mushroom body and then the lateral horn, the GH146-labelled neurons of ALv1 (as well as the otd−/− ALv1) largely innervate only the lateral horn. The otd−/− LALv1 lineage was also recovered along with each of the three antennal lobe lineages, and in one case all three known GH146-Gal4 labelled antennal lobe lineages (ALad1, ALl1 and ALv1) were recovered along with it, resulting in four distinct GH146-Gal4 labelled lineages in the brain (Figure 5A–C).10.7554/eLife.04407.010Figure 5.Loss of otd from the LALv1 lineage results in an extra, fourth antennal lobe lineage labelled by the GH146 enhancer.


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 an extra, fourth antennal lobe lineage labelled by the GH146 enhancer.(A–C) document a MARCM clonal brain, in which the clones  for otd function and are labelled by the GH146-Gal4. In this brain, the three known antennal lobe lineages normally labelled by GH146-Gal4 (ALad1, ALl1, and Alv1) have been recovered, along with an additional fourth neuroblast lineage, LALv1. (D–G) document a control brain where Otd is not down regulated in the LALv1 lineage (yellow dotted lines in E). In this brain, there are three clusters of antennal lobe projection neurons labelled by GH146-QF corresponding to the ALad1, ALl1 and ALv1 lineages, magenta dotted lines in D and G). (H–K) show a brain in which there has been efficient knock down of Otd in the LALv1 lineage (note loss of Otd immunolabelling ventral to the antennal lobe; yellow dotted lines in I). In this brain, apart from the ALad1, ALl1, and ALv1 projection neurons, an additional, fourth cluster of cells is seen innervating the antennal lobe (‘4’, LALv1). The yellow asterisks in A, D, H indicate the point of entry of the ALv1 lineage into the antennal lobe, and the yellow arrow indicates its axon tract. The magenta asterisks in A, D, H indicate the point of entry of the LALv1 lineage into the antennal lobe, and the magenta arrow indicates its axon tract. Note that these are distinct from each other. Genotype in A–C: FRT19A,otdYH13/FRT19A,Tub-Gal80,hsFLP; GH146-Gal4,UAS-mCD8::GFP/+. Genotype in D–K: UASdicer/+;Insc-Gal4/UAS-miRNA-otd-1;GH146-QF,QUAS-mtdTomato-HA/+). Scale bars are 50 µm. The one in A is applicable to B and C and the one in in D is applicable to D–K. Yellow line represents the midline.DOI:http://dx.doi.org/10.7554/eLife.04407.010
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Related In: Results  -  Collection

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

fig5: Loss of otd from the LALv1 lineage results in an extra, fourth antennal lobe lineage labelled by the GH146 enhancer.(A–C) document a MARCM clonal brain, in which the clones for otd function and are labelled by the GH146-Gal4. In this brain, the three known antennal lobe lineages normally labelled by GH146-Gal4 (ALad1, ALl1, and Alv1) have been recovered, along with an additional fourth neuroblast lineage, LALv1. (D–G) document a control brain where Otd is not down regulated in the LALv1 lineage (yellow dotted lines in E). In this brain, there are three clusters of antennal lobe projection neurons labelled by GH146-QF corresponding to the ALad1, ALl1 and ALv1 lineages, magenta dotted lines in D and G). (H–K) show a brain in which there has been efficient knock down of Otd in the LALv1 lineage (note loss of Otd immunolabelling ventral to the antennal lobe; yellow dotted lines in I). In this brain, apart from the ALad1, ALl1, and ALv1 projection neurons, an additional, fourth cluster of cells is seen innervating the antennal lobe (‘4’, LALv1). The yellow asterisks in A, D, H indicate the point of entry of the ALv1 lineage into the antennal lobe, and the yellow arrow indicates its axon tract. The magenta asterisks in A, D, H indicate the point of entry of the LALv1 lineage into the antennal lobe, and the magenta arrow indicates its axon tract. Note that these are distinct from each other. Genotype in A–C: FRT19A,otdYH13/FRT19A,Tub-Gal80,hsFLP; GH146-Gal4,UAS-mCD8::GFP/+. Genotype in D–K: UASdicer/+;Insc-Gal4/UAS-miRNA-otd-1;GH146-QF,QUAS-mtdTomato-HA/+). Scale bars are 50 µm. The one in A is applicable to B and C and the one in in D is applicable to D–K. Yellow line represents the midline.DOI:http://dx.doi.org/10.7554/eLife.04407.010
Mentions: The cell body position of this type of otd−/− clone as well as the entry point of its tract into the antennal lobe (both ventro-medial) did not correspond to any of the known GH146-Gal4 labelled antennal lobe lineages (Ito et al., 2013; Yu et al., 2013). Importantly, this is also true for the ALv1 lineage, whose cell bodies are also located ventral to the antennal lobe; despite the ventral cell body position of the LALv1 and ALv1 lineages, their overall neuroanatomy is very different from each other. The neurites of the otd−/− LALv1 lineage enter the lobe medially (magenta asterisk in Figure 5A,D,H) while the neurites of the ALv1 (as well as the otd−/− ALv1) enter it laterally (yellow asterisk in Figure 5A,D,H). Moreover, while the otd−/− LALv1 lineage uses the medial antennal lobe tract (magenta arrow in Figure 5A,D,H), the ALv1 (as well as the otd−/− ALv1) uses the mediolateral antennal lobe tract (yellow arrow in Figure 5A,C). Finally, while the otd−/− LALv1 lineage first innervates the calyx of the mushroom body and then the lateral horn, the GH146-labelled neurons of ALv1 (as well as the otd−/− ALv1) largely innervate only the lateral horn. The otd−/− LALv1 lineage was also recovered along with each of the three antennal lobe lineages, and in one case all three known GH146-Gal4 labelled antennal lobe lineages (ALad1, ALl1 and ALv1) were recovered along with it, resulting in four distinct GH146-Gal4 labelled lineages in the brain (Figure 5A–C).10.7554/eLife.04407.010Figure 5.Loss of otd from the LALv1 lineage results in an extra, fourth antennal lobe lineage labelled by the GH146 enhancer.

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