New research reveals how development and sex shape the brain

Researchers from the University of Oxford have created the first high-resolution molecular atlas of the adult Drosophila melanogaster (common fruit fly) brain, uncovering how the neurons that drive behaviour in adults retain a record of their developmental origins. A companion study, released in parallel, shows how these same developmental programs are selectively reused and modified by sex to generate male and female behavioural diversity.

Together, these papers provide a new framework for understanding how the brain’s architecture arises and evolves, from its developmental blueprint to its functional specialisation.

The work, led by Professor Stephen Goodwin’s group in Oxford’s Department of Physiology, Anatomy and Genetics (DPAG), offers an unprecedented view of neuronal diversity. By integrating multiple single-cell RNA sequencing datasets, the researchers achieved tenfold coverage of the Drosophila central brain, capturing transcriptional information for nearly every individual neuron.

Surprisingly, the team found that the genetic diversity of neurons is far greater than previously thought, with many cell types represented by only a single neuron per hemisphere. Their analyses suggest that transcriptomic and anatomical identities represent complementary and equally informative axes for defining neuronal types. This insight provides a crucial link between molecular diversity and the physical wiring of the brain, bridging developmental and systems-level perspectives.

'Our results show that the adult brain carries a molecular record of how it was built,' said Professor Goodwin. 'We can now see that the diversity of neurons, and therefore of behaviours, emerges from a simple developmental logic based on lineage, timing, and selective differentiation.'

The companion paper extends these principles to sexual dimorphism, revealing that male and female brains use the same developmental templates in different ways. Rather than separate male and female circuits, the team found that sex differences arise through selective neuronal survival within shared lineages. Female-biased neurons tend to be born early, while male-biased neurons emerge later, indicating that sex leverages distinct developmental windows to shape behaviour.

'This shows how evolution can create new behavioural capabilities without rebuilding the brain from scratch,' said lead author Dr. Erin Allen. 'Sex doesn’t reinvent the wiring; it tweaks when and which neurons persist.'

These findings not only redefine the developmental logic of the fly brain but also provide essential parameters for computational and systems neuroscience. By revealing how molecular and anatomical classifications intersect, the atlas offers a foundation for modelling brain organisation and function.

The Goodwin group has also created a user-friendly website featuring interactive visualisations of the atlases referenced in these studies, allowing researchers to explore the data directly. This work was supported by the Wellcome Trust and the Biotechnology and Biological Sciences Research Council.

Both papers, 'A High-Resolution Atlas of the Brain Predicts Lineage and Birth Order Underlie Neuronal Identity' and 'Differential Neuronal Survival Defines a Novel Axis of Sexual Dimorphism in the Drosophila Brain', are published in Cell Genomics.