By Rachel Scanza, Ph.D.

While biologists tend to characterize the type and function of cells based on which genes are active, recent neurobiology research highlights the complexity of classifying cell type based on gene activity alone. A recent article authored by Stowers Institute Assistant Investigator Neşet Özel, Ph.D., and Professor of Biology and Neural Science Claude Desplan, Ph.D., from New York University discusses current findings that challenge this gene-focused notion based on the fact that some neurons, despite nearly identical gene expression, have very different roles.

Published in Nature News & Views on February 12, 2025, the article comments on the researchers’ question of whether a cell’s gene expression necessarily defines its function. Part of the problem is practicality. Testing the function of every cell — around 30 trillion in humans — is unrealistic. Compounding this is that neuronal function and gene expression can change from development to adulthood.

A recent study used a combination of three powerful technologies — single cell RNA sequencing, hybridization chain reaction, and calcium imaging — to distinguish neuronal types both by gene expression, spatial location, and functional responses within a visual processing region of the zebrafish brain. The team found measurable functional and anatomical diversity in molecularly identical neurons, potentially due to the presence of nearby neurons and molecules that influence how connections are formed through which information is sent and received.

Özel and Desplan explain that these results support the notion that cell type may define a neuron’s potential function rather than comprehensively determining it. However, they highlight limitations of the study — the researchers may not have been able to resolve all diversity in gene expression. In addition, because current estimates of the number of cell types in the human brain vary drastically, the authors suggest that profiling protein activity within single cells may be a better method for fully understanding the molecular identity and diversity of neurons.

At the Stowers Institute, the Özel Lab is actively investigating brain development in the region that processes vision in the fruit fly, Drosophila melanogaster. The lab seeks to understand the mechanisms for how genes are regulated during the development and specialization of neurons. Genetic techniques and computational models are being used to answer fundamental questions on how the brain develops, which ultimately may help uncover mechanisms underlying neurodevelopmental disorders.