Systematic analysis of neural projections reveals clonal composition of the Drosophila brain
Open accessAbstract
Background During development neurons are generated by sequential divisions of neural stem cells, or neuroblasts. In the insect brain progeny of certain stem cells form lineage-specific sets of projections that arborize in distinct brain regions, called clonal units. Though this raises the possibility that the entire neural network in the brain might be organized in a clone-dependent fashion, only a small portion of clones has been identified. Results Using Drosophila melanogaster, we randomly labeled one of about 100 stem cells at the beginning of the larval stage, analyzed the projection patterns of their progeny in the adult, and identified 96 clonal units in the central part of the fly brain, the cerebrum. Neurons of all the clones arborize in distinct regions of the brain, though many clones feature heterogeneous groups of neurons in terms of their projection patterns and neurotransmitters. Arborizations of clones overlap preferentially to form several groups of closely associated clones. Fascicles and commissures were all made by unique sets of clones. Whereas well-investigated brain regions such as the mushroom body and central complex consist of relatively small numbers of clones and are specifically connected with a limited number of neuropils, seemingly disorganized neuropils surrounding them are composed by a much larger number of clones and have extensive specific connections with many other neuropils. Conclusions Our study showed that the insect brain is formed by a composition of cell-lineage-dependent modules. Clonal analysis reveals organized architecture even in those neuropils without obvious structural landmarks.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Our lineage-associated tracts have been mapped by light microscopy and assigned to named lineage clones.
“Our lineage-associated tracts have been mapped by light microscopy and assigned to named lineage clones.139,199,200,201,202”
From Neurotransmitter classification from electron microscopy images at synaptic sites in Drosophila melanogaster (2024) · cites this paper as [139]
From light-level data that labels a whole lineage and all of its hemilineages together, it is occasionally difficult to assess whether there is a single hemilineage or multiple if the cell body clusters do not separate sufficiently.
“From light-level data that labels a whole lineage and all of its hemilineages together,139,199,200,201 it is occasionally difficult to assess whether there is a single hemilineage or multiple, if the cell body clusters happen to not separate sufficiently.”
From Neurotransmitter classification from electron microscopy images at synaptic sites in Drosophila melanogaster (2024) · cites this paper as [139]
Previous literature expected a total of around 119 lineages in the central brain, including the gnathal ganglia (GNG).
“From previous literature, we expected a total of around 119 lineages in the central brain, including the gnathal ganglia (GNG)31–34,84.”
From Whole-brain annotation and multi-connectome cell typing of Drosophila (2024) · cites this paper as [33]
The following lineages are new to the Ito/Lee nomenclature: CREl1/DALv3, LHp3/CP5, DILP/DILP, LALa1/BAlp2, SMPpm1/DPMm2 and VLPl5/BLVa3_or_4.
“new to refs. 33,34 (ItoLee nomenclature) are: CREl1/DALv3, LHp3/CP5, DILP/DILP, LALa1/BAlp2, SMPpm1/DPMm2 and VLPl5/BLVa3_or_4”
From Whole-brain annotation and multi-connectome cell typing of Drosophila (2024) · cites this paper as [33]
The AOTUv1_ventral/DALcm2_ventral hemilineage seems to be missing in the AOTUv1/DALcm2 clone in the Ito collection.
“For example, the AOTUv1_ventral/DALcm2_ventral hemilineage seems to be missing in the AOTUv1/DALcm2 clone in the Ito collection33.”
From Whole-brain annotation and multi-connectome cell typing of Drosophila (2024) · cites this paper as [33]
Light-level clones from refs. 33,34 match very well the great majority of the time.
“although light-level clones from refs. 33,34 match very well the great majority of the time”
From Whole-brain annotation and multi-connectome cell typing of Drosophila (2024) · cites this paper as [33]
Comparing the location, trajectory, and the combined arborization patterns of all the neurons that arise from a particular CBF with the light microscopy (LM) image data of the neuronal progeny that derive from single neuroblasts (Ito et al., 2013; Yu et al., 2013), we confirmed that the neurons of each CBF group belong to a single lineage.
“Comparing the location, trajectory, and the combined arborization patterns of all the neurons that arise from a particular CBF with the light microscopy (LM) image data of the neuronal progeny that derive from single neuroblasts (Ito et al., 2013; Yu et al., 2013), we confirmed that the neurons of each CBF group belong to a single lineage.”
From A connectome and analysis of the adult Drosophila central brain (2020) · cites this paper as Ito et al., 2013
Among the 192 bundles, 155 matched the CBF bundles of 92 known and six newly identified clonal units (Ito et al., 2013; Yu et al., 2013).
“Among the 192 bundles, 155 matched the CBF bundles of 92 known and six newly identified clonal units (Ito et al., 2013; Yu et al., 2013), a population of neurons and neuronal circuits derived from a single stem cell.”
From A connectome and analysis of the adult Drosophila central brain (2020) · cites this paper as Ito et al., 2013
Cites
Finding and evaluating community structure in networks
Newman, M. E. J., & Girvan, M. (2004) · Physical Review E · doi:10.1103/physreve.69.026113 · Cited by 13,931 · see citing works
Bello, B. C., Izergina, N., Caussinus, E., & Reichert, H. (2008) · Neural Development · doi:10.1186/1749-8104-3-5 · Cited by 388 · see citing works
Otsuna, H., & Ito, K. (2006) · The Journal of Comparative Neurology · doi:10.1002/cne.21015 · Cited by 224 · see citing works
Self-citationClonal Development and Organization of the Adult Drosophila Central Brain
Yu, H.-H., Awasaki, T., Schroeder, M. D., Long, F., Yang, J. S., He, Y., Ding, P., Kao, J.-C., Wu, G. Y.-Y., Peng, H., et al. (2013) · Current Biology · doi:10.1016/j.cub.2013.02.057 · Cited by 163 · see citing works
Clonal production and organization of inhibitory interneurons in the neocortex
Brown, K. N., Chen, S., Han, Z., Lu, C.-H., Tan, X., Zhang, X.-J., Ding, L., Lopez-Cruz, A., Saur, D., Anderson, S. A., et al. (2011) · Science · doi:10.1126/science.1208884 · Cited by 152 · see citing works
Gamma‐aminobutyric acid (GABA)‐mediated neural connections in the <i>Drosophila</i> antennal lobe
Okada, R., Awasaki, T., & Ito, K. (2009) · Journal of Comparative Neurology · doi:10.1002/cne.21971 · Cited by 146 · see citing works
Self-citationIdentification of midbrain floor plate radial glia-like cells as dopaminergic progenitors
Bonilla, S., Hall, A. C., Pinto, L., Attardo, A., Götz, M., Huttner, W. B., & Arenas, E. (2008) · Glia · doi:10.1002/glia.20654 · Cited by 136 · see citing works
Miyazaki, T., & Ito, K. (2010) · Journal of Comparative Neurology · doi:10.1002/cne.22433 · Cited by 83 · see citing works
Self-citationDas, A., Chiang, A., Davla, S., Priya, R., Reichert, H., VijayRaghavan, K., & Rodrigues, V. (2011) · Neural Systems & Circuits · doi:10.1186/2042-1001-1-4 · Cited by 38 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
A connectome and analysis of the adult Drosophila central brain
Scheffer, L. K., Xu, C. S., Januszewski, M., Lu, Z., Takemura, S.-Y., Hayworth, K. J., Huang, G. B., Shinomiya, K., Maitlin-Shepard, J., Berg, S., et al. (2020) · eLife · doi:10.7554/elife.57443 · Cited by 1,128 · see citing works
Self-citationA Single-Cell Transcriptome Atlas of the Aging Drosophila Brain
Davie, K., Janssens, J., Koldere, D., De Waegeneer, M., Pech, U., Kreft, Ł., Aibar, S., Makhzami, S., Christiaens, V., Bravo González-Blas, C., et al. (2018) · Cell · doi:10.1016/j.cell.2018.05.057 · Cited by 840 · see citing works
A Systematic Nomenclature for the Insect Brain
Ito, K., Shinomiya, K., Ito, M., Armstrong, J. D., Boyan, G., Hartenstein, V., Harzsch, S., Heisenberg, M., Homberg, U., Jenett, A., et al. (2014) · Neuron · doi:10.1016/j.neuron.2013.12.017 · Cited by 611 · see citing works
Self-citationWhole-brain annotation and multi-connectome cell typing of Drosophila
Schlegel, P., Yin, Y., Bates, A. S., Dorkenwald, S., Eichler, K., Brooks, P., Han, D. S., Gkantia, M., dos Santos, M., Munnelly, E. J., et al. (2024) · Nature · doi:10.1038/s41586-024-07686-5 · Cited by 413 · see citing works
“33 into account for the total count of lineages/hemilineages, because they originate in the optic lobe and their neuroblast of origin has not been clearly demonstrated in the larva: VPNd2, VPNd3, VPNd4, VPNp2, VPNp3, VPNp4, VPNv1, VPNv2 and VPNv3.”
BackgroundMethodInfluentialWu, M., Nern, A., Williamson, W. R., Morimoto, M. M., Reiser, M. B., Card, G. M., & Rubin, G. M. (2016) · eLife · doi:10.7554/elife.21022 · Cited by 304 · see citing works
The functional organization of descending sensory-motor pathways in Drosophila
Namiki, S., Dickinson, M. H., Wong, A. M., Korff, W., & Card, G. M. (2018) · eLife · doi:10.7554/elife.34272 · Cited by 337 · see citing works
The natverse, a versatile toolbox for combining and analysing neuroanatomical data
Bates, A. S., Manton, J. D., Jagannathan, S. R., Costa, M., Schlegel, P., Rohlfing, T., & Jefferis, G. S. (2020) · eLife · doi:10.7554/elife.53350 · Cited by 215 · see citing works
Eckstein, N., Bates, A. S., Champion, A., Du, M., Yin, Y., Schlegel, P., Lu, A. K.-Y., Rymer, T., Finley-May, S., Paterson, T., et al. (2024) · Cell · doi:10.1016/j.cell.2024.03.016 · Cited by 233 · see citing works
“In these studies, the authors had already linked some of their reconstructed cell types to immunohistochemical data (Aso et al., 2014; Bräcker et al., 2013; Busch et al., 2009; Davis et al., 2018; Dolan et al., 2019; Ito et al., 2013; Lai et al., 2008; Okada et al., 2009; Shinomiya et al., 2015; Tanaka et al., 2012; W…”
Information flow, cell types and stereotypy in a full olfactory connectome
Schlegel, P., Bates, A. S., Stürner, T., Jagannathan, S. R., Drummond, N., Hsu, J., Serratosa Capdevila, L., Javier, A., Marin, E. C., Barth-Maron, A., et al. (2021) · eLife · doi:10.7554/elife.66018 · Cited by 178 · see citing works
Clonal Development and Organization of the Adult Drosophila Central Brain
Yu, H.-H., Awasaki, T., Schroeder, M. D., Long, F., Yang, J. S., He, Y., Ding, P., Kao, J.-C., Wu, G. Y.-Y., Peng, H., et al. (2013) · Current Biology · doi:10.1016/j.cub.2013.02.057 · Cited by 163 · see citing works
Neuron hemilineages provide the functional ground plan for the Drosophila ventral nervous system
Harris, R. M., Pfeiffer, B. D., Rubin, G. M., & Truman, J. W. (2015) · eLife · doi:10.7554/elife.04493 · Cited by 125 · see citing works
“The recent characterization of lineages in the fly brain (Ito et al., 2013; Yu et al., 2013) shows many brain lineages that contain a greater diversity of cell types than we see for the VNS hemilineages.”
Eckstein, N., Bates, A. S., Champion, A., Du, M., Yin, Y., Schlegel, P., Lu, A. K.-Y., Rymer, T., Finley-May, S., Paterson, T., et al. (2020) · doi:10.1101/2020.06.12.148775 · Cited by 115 · see citing works
Marin, E. C., Büld, L., Theiss, M., Sarkissian, T., Roberts, R. J. V., Turnbull, R., Tamimi, I. F. M., Pleijzier, M. W., Laursen, W. J., Drummond, N., et al. (2020) · Current Biology · doi:10.1016/j.cub.2020.06.028 · Cited by 121 · see citing works
Schlegel, P., Yin, Y., Bates, A. S., Dorkenwald, S., Eichler, K., Brooks, P., Han, D. S., Gkantia, M., dos Santos, M., Munnelly, E. J., et al. (2023) · doi:10.1101/2023.06.27.546055 · Cited by 102 · see citing works
Functional and anatomical specificity in a higher olfactory centre
Frechter, S., Bates, A. S., Tootoonian, S., Dolan, M.-J., Manton, J., Jamasb, A. R., Kohl, J., Bock, D., & Jefferis, G. (2019) · eLife · doi:10.7554/elife.44590 · Cited by 105 · see citing works
Comparative Neuroanatomy of the Lateral Accessory Lobe in the Insect Brain
Namiki, S., & Kanzaki, R. (2016) · Frontiers in Physiology · doi:10.3389/fphys.2016.00244 · Cited by 78 · see citing works
Neural circuit mechanisms for steering control in <i>walking Drosophila</i>
Rayshubskiy, A., Holtz, S. L., Bates, A. S., Vanderbeck, Q. X., Capdevila, L. S., Rockwell, V., & Wilson, R. I. (2020) · doi:10.1101/2020.04.04.024703 · Cited by 64 · see citing works
Matsuo, E., Seki, H., Asai, T., Morimoto, T., Miyakawa, H., Ito, K., & Kamikouchi, A. (2016) · Journal of Comparative Neurology · doi:10.1002/cne.23955 · Cited by 56 · see citing works
Self-citationConservation and divergence of related neuronal lineages in the Drosophila central brain
Lee, Y.-J., Yang, C.-P., Miyares, R. L., Huang, Y.-F., He, Y., Ren, Q., Chen, H.-M., Kawase, T., Ito, M., Otsuna, H., et al. (2020) · eLife · doi:10.7554/elife.53518 · Cited by 60 · see citing works
Self-citationLovick, J. K., Ngo, K. T., Omoto, J. J., Wong, D. C., Nguyen, J. D., & Hartenstein, V. (2013) · Developmental Biology · doi:10.1016/j.ydbio.2013.07.008 · Cited by 48 · see citing works
Hartenstein, V., Omoto, J. J., Ngo, K. T., Wong, D., Kuert, P. A., Reichert, H., Lovick, J. K., & Younossi‐Hartenstein, A. (2018) · Journal of Comparative Neurology · doi:10.1002/cne.24287 · Cited by 31 · see citing works
The development and assembly of the Drosophila adult ventral nerve cord
Venkatasubramanian, L., & Mann, R. S. (2019) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2019.01.013 · Cited by 28 · see citing works
Asymmetric activity of NetrinB controls laterality of the Drosophila brain
Lapraz, F., Boutres, C., Fixary-Schuster, C., De Queiroz, B. R., Plaçais, P. Y., Cerezo, D., Besse, F., Préat, T., & Noselli, S. (2023) · Nature Communications · doi:10.1038/s41467-023-36644-4 · Cited by 25 · see citing works
- Authors
- Ito, M., Masuda, N., Shinomiya, K., Endo, K., & Ito, K.
- Affiliations
- The University of Tokyo (JP)
- Corresponding author
- Ito, Kei
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2013-04
- Volume
- 23
- Issue
- 8
- Pages
- 644-655
- ISSN
- 0960-9822 (ISSN-L)
- OpenAlex
- W2005735307
- Cited by
- 166
- References
- 9
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 9 · 2023: 18 · 2022: 7 · 2021: 8 · 2020: 15 · 2019: 11 · 2018: 8 · 2017: 23 · 2016: 11 · 2015: 12 · 2014: 20 · 2013: 8
- FWCI
- 8.31
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 386 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Core Research for Evolutional Science and Technology
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Science and Technology Agency
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- neural stem cells, neuroblast lineage, Drosophila melanogaster brain, cerebrum, neuronal projections, axonal arborization, commissures, mushroom body, central complex, neuropil
- MeSH terms
- Animals, Brain, Clone Cells, Drosophila melanogaster, Female, Larva, Microscopy, Confocal, Cell Lineage, Neuropil, Neural Stem Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
