Conservation and divergence of related neuronal lineages in the Drosophila central brain
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Abstract
Wiring a complex brain requires many neurons with intricate cell specificity, generated by a limited number of neural stem cells. Drosophila central brain lineages are a predetermined series of neurons, born in a specific order. To understand how lineage identity translates to neuron morphology, we mapped 18 Drosophila central brain lineages. While we found large aggregate differences between lineages, we also discovered shared patterns of morphological diversification. Lineage identity plus Notch-mediated sister fate govern primary neuron trajectories, whereas temporal fate diversifies terminal elaborations. Further, morphological neuron types may arise repeatedly, interspersed with other types. Despite the complexity, related lineages produce similar neuron types in comparable temporal patterns. Different stem cells even yield two identical series of dopaminergic neuron types, but with unrelated sister neurons. Together, these phenomena suggest that straightforward rules drive incredible neuronal complexity, and that large changes in morphology can result from relatively simple fating mechanisms.
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'LALv1' is one of few hemilineages whose birth order has been delineated.
“‘LALv1’ is, fortunately, one of few hemilineages whose birth order has been delineated.102”
From Neurotransmitter classification from electron microscopy images at synaptic sites in Drosophila melanogaster (2024) · cites this paper as [102]
The Results section (“Hemilineages vary greatly in gross complexity,” Figure 7; page not given) arranges LALv1A and LALv1B neuron types in birth order, supporting that their birth order has been delineated. The cited passages do not establish that LALv1 is one of only a few hemilineages for which this has been done. (LLM, conf=0.82)
Experimental — accuracy not yet measuredWe were able to map the transmission-morphotype switch in LALv1 ventral into its developmental sequence.
“Because a recent analysis delineated the birth order of LALv1 neurons,102 we were able to map this transmission-morphotype switch into its developmental sequence (Figure 7F, lower).”
From Neurotransmitter classification from electron microscopy images at synaptic sites in Drosophila melanogaster (2024) · cites this paper as [102]
Cases have been identified where a single lineage-associated tract is composed of two hemilineages.
“It should be noted that cases have been identified102 where a single lineage-associated tract is composed of two hemilineages.”
From Neurotransmitter classification from electron microscopy images at synaptic sites in Drosophila melanogaster (2024) · cites this paper as [102]
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Self-citationA High-Resolution Atlas of the Brain Predicts Lineage and Birth Order Underly Neuronal IdentityPreprint
Allen, A. M., Neville, M. C., Nojima, T., Alejevski, F., Agarwal, D., Sims, D., & Goodwin, S. F. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.06.04.657818 · Cited by 2 · see citing works
Toward a probabilistic definition of neural cell types
Andriatsilavo, M., & Hassan, B. A. (2025) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2025.103035 · Cited by 1 · see citing works
Sequential formation of Drosophila circuit asymmetry via prolonged structural plasticity
Markovitsch, J., Mitić, D., Jiménez-García, A., Alsberga, Z., Kainz, S., Kaur, R., & Hummel, T. (2026) · Science Advances · doi:10.1126/sciadv.aea6020 · Cited by 1 · see citing works
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Deng, X., & Zhu, S. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.10.29.620860 · Cited by 1 · see citing works
Farnworth, M., Bucher, G., & Hartenstein, V. (2021) · bioRxiv · doi:10.1101/2021.11.30.470557 · Cited by 16 · see citing works
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Non-autonomous Vnd acts with autonomous Appl during mushroom body axon growth in DrosophilaPreprint
Marquilly, C., Boulanger, A., Busto, G. U., Zinzen, R. P., Hassan, B. A., Fradkin, L. G., & Dura, J. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.09.01.555727
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Slit regulates subcellular-specific targeting of dendrites and axons in the Drosophila brainPreprint
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Lineage Analysis at Single-Cell Resolution by Twin-Spot MARCM with Lineage-Restricted Drivers
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Self-citationStriking parallels between the dopaminergic systems of flies and mammals
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Amyloid precursor protein ortholog Appl acts with Vnd during mushroom body axon growth in Drosophila
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Marin, E. C., Lacin, H., Moon, S. S., Cachero, S., Freehling, G. E. H., Bell, K. E., Depenbusch, E. E., Patterson, A. M., Pai, A., Morris, B. J., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.10.13.758796
- Authors
- 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., Sugino, K., Aso, Y., Ito, K., & Lee, T.
- Affiliations
- Howard Hughes Medical Institute (US)
- Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
- Corresponding author
- Lee, Tzumin
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2020-04-07
- Volume
- 9
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC7173964
- OpenAlex
- W3014749649
- Cited by
- 60
- References
- 50
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 8 · 2023: 20 · 2022: 3 · 2021: 4 · 2020: 7 · 2019: 1
- FWCI
- 2.76
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Howard Hughes Medical Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Keywords
- neural stem cells, Notch signaling, neuronal morphology, dopaminergic neurons, neuronal heterogeneity, neurogenesis
- MeSH terms
- Animals, Brain, Drosophila melanogaster, Larva, Neurons, Cell Lineage, Neurogenesis, Neural Stem Cells
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