A global molecular code for birth order and neuronal identity in Drosophila
9 affiliations
- 1Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, UK. [email protected]
- 2Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, UK
- 3Department of Zoology, University of Cambridge, Cambridge, UK
- 4Aelysia, Bristol, UK
- 5Division of Biological and Biomedical Systems, School of Science and Engineering, University of Missouri-Kansas City, Kansas City, MO, USA
- 6Department of Zoology, University of Cambridge, Cambridge, UK. [email protected]
- 7Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, UK. [email protected]
- 8Institute of Neuroscience, Consiglio Nazionale delle Ricerche (CNR), Vedano al Lambro, Italy. [email protected]
- 9Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, UK. [email protected]
Abstract
The assembly of functional neural circuits relies on the generation of diverse neural types with precise molecular identity and connectivity. Unlocking general principles of neuronal specification and wiring across the nervous system requires a systematic and high-resolution characterization of its diversity, recently enabled by advances in single-cell transcriptomics and connectomics. However, linking the molecular identity of neurons to circuit architecture remains a key challenge. Here we present a high-resolution developmental transcriptional atlas for the Drosophila melanogaster nerve cord, the central hub for sensory–motor circuits. With a considerable 38× aggregate coverage relative to its reference connectome 1,2 , our atlas captures extensive molecular diversity and enables robust alignment to the adult connectome. We identified three developmental principles underlying neuronal diversity in the nerve cord. First, the timing of neurogenesis shapes diversification of molecular identity: embryonic-born neurons diverge faster than larval-born neurons, as also observed in the adult connectome. Second, 17 transcription factors common to neurons from all lineages provide a global molecular identity code for birth order. Lastly, by mapping sex-specific transcriptional profiles to the connectome, we identified female-specific apoptosis and transcriptional divergence as key global drivers of sex specification. By revealing key organizational axes of molecular identity, this atlas opens avenues to dissect the molecular mechanisms underpinning the development and evolution of neural circuits.
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BibTeX
@article{cachero2026global,
title = {{A global molecular code for birth order and neuronal identity in Drosophila}},
author = {Sebastian Cachero and Myrto Mitletton and Isabella R. Beckett and Elizabeth C. Marin and Laia Serratosa Capdevila and Marina Gkantia and Jelly HM Soffers and Haluk Lacin and Gregory S.X.E. Jefferis and Erika Doná},
journal = {Nature},
year = {2026},
month = jul,
doi = {10.1038/s41586-026-10797-w},
url = {https://doi.org/10.1038/s41586-026-10797-w},
note = {CC BY},
}
RIS
TY - JOUR
TI - A global molecular code for birth order and neuronal identity in Drosophila
AU - Sebastian Cachero
AU - Myrto Mitletton
AU - Isabella R. Beckett
AU - Elizabeth C. Marin
AU - Laia Serratosa Capdevila
AU - Marina Gkantia
AU - Jelly HM Soffers
AU - Haluk Lacin
AU - Gregory S.X.E. Jefferis
AU - Erika Doná
PY - 2026
DA - 2026/07/22
JO - Nature
DO - 10.1038/s41586-026-10797-w
UR - https://doi.org/10.1038/s41586-026-10797-w
AB - The assembly of functional neural circuits relies on the generation of diverse neural types with precise molecular identity and connectivity. Unlocking general principles of neuronal specification and wiring across the nervous system requires a systematic and high-resolution characterization of its diversity, recently enabled by advances in single-cell transcriptomics and connectomics. However, linking the molecular identity of neurons to circuit architecture remains a key challenge. Here we present a high-resolution developmental transcriptional atlas for the Drosophila melanogaster nerve cord, the central hub for sensory–motor circuits. With a considerable 38× aggregate coverage relative to its reference connectome 1,2 , our atlas captures extensive molecular diversity and enables robust alignment to the adult connectome. We identified three developmental principles underlying neuronal diversity in the nerve cord. First, the timing of neurogenesis shapes diversification of molecular identity: embryonic-born neurons diverge faster than larval-born neurons, as also observed in the adult connectome. Second, 17 transcription factors common to neurons from all lineages provide a global molecular identity code for birth order. Lastly, by mapping sex-specific transcriptional profiles to the connectome, we identified female-specific apoptosis and transcriptional divergence as key global drivers of sex specification. By revealing key organizational axes of molecular identity, this atlas opens avenues to dissect the molecular mechanisms underpinning the development and evolution of neural circuits.
SN - 0028-0836
SN - 1476-4687
ER -