Biology subjects

Neville, M. C.

Publications and source records attributed to Neville, M. C..

4 recordsLinked to original sources

bioRxiv2025

A High-Resolution Atlas of the Brain Predicts Lineage and Birth Order Underly Neuronal Identity.

Gene expression shapes the nervous system at every biological level, from molecular and cellular processes defining neuronal identity and function to systems-level wiring and circuit dynamics underlying behaviour. Here, we generate the first high-resolution, single-cell transcriptomic atlas of the adult Drosophila melanogaster central brain by integrating multiple datasets, achieving an unprecedented tenfold coverage of every neuron in this complex tissue. We show that a neurons genetic identity overwhelmingly reflects its developmental origin, preserving a genetic address based on both lineage and birth order. We reveal foundational rules linking neurogenesis to transcriptional identity and provide a framework for systematically defining neuronal types. This atlas provides a powerful resource for mapping the cellular substrates of behaviour by integrating annotations of hemilineage, cell types/subtypes and molecular signatures of underlying physiological properties. It lays the groundwork for a long-sought bridge between developmental processes and the functional circuits that give rise to behaviour.

neuroscience↗

bioRxiv2025

A Role for Exaptation in Sculpting Sexually Dimorphic Brains from Shared Neural Lineages.

Sex differences in behaviours arise from variations in female and male nervous systems, yet the cellular and molecular bases of these differences remain poorly defined. Here, we take an unbiased, single-cell transcriptomic approach to uncover how sex shapes the adult Drosophila melanogaster brain. We show that sex differences do not result from large-scale transcriptional reprogramming but through fine-tuning of otherwise shared developmental templates via the sex-differentiating transcription factors Doublesex and Fruitless. We reveal, with unprecedented resolution, the extraordinary genetic diversity within these sexually dimorphic cell types and find birth order represents a novel axis of sexual differentiation. Neuronal identity in the adult reflects spatiotemporal patterning and sex-specific survival, with female-biased neurons arising early and male-biased neurons arising late. This pattern reframes dimorphic neurons as "paralogous" rather than "orthologous", suggesting sex leverages distinct developmental windows to build behavioural circuits and highlights a role for exaptation in diversifying the brain.

neuroscience↗

bioRxiv2022

Low-level repressive histone marks fine-tune stemness gene transcription in neural stem cells

Coordinated regulation of stemness gene activity by transcriptional and translational mechanisms poise stem cells for a timely cell-state transition during differentiation. Although important for all stemness-to-differentiation transitions, mechanistic understanding of the fine-tuning of stemness gene transcription is lacking due to the compensatory effect of translational control. We used intermediate neural progenitor (INP) identity commitment to define the mechanisms that fine-tune stemness gene transcription in fly neural stem cells (neuroblasts). We demonstrate that the transcription factor FruitlessC (FruC) binds cis-regulatory elements of most genes uniquely transcribed in neuroblasts. Loss of fruC function alone has no effect on INP commitment but drives INP dedifferentiation when translational control is reduced. FruC negatively regulates gene expression by promoting low-level enrichment of the repressive histone mark H3K27me3 in gene cis-regulatory regions. Identical to fruC loss-of-function, reducing Polycomb Repressive Complex 2 activity increases stemness gene activity. We propose low-level H3K27me3 enrichment fine-tunes stemness gene transcription in stem cells, a mechanism likely conserved from flies to humans.

developmental biology↗

bioRxiv2019

A single-cell transcriptomic atlas of the adult Drosophila ventral nerve cord

The Drosophila ventral nerve cord (VNC) receives and processes descending signals from the brain to produce a variety of coordinated locomotor outputs. It also integrates sensory information from the periphery and sends ascending signals to the brain. We used single-cell transcriptomics to generate an unbiased classification of cellular diversity in the VNC of five-day old adult flies. We produced an atlas of 26,000 high-quality cells, representing more than 100 transcriptionally distinct cell types. The predominant gene signatures defining neuronal cell types reflect shared developmental histories based on the neuroblast from which cells were derived, as well as their birth order. Cells could also be assigned to specific neuromeres using adult Hox gene expression. This single-cell transcriptional atlas of the adult fly VNC will be a valuable resource for future studies of neurodevelopment and behavior.

neuroscience↗