Mouse and human share conserved transcriptional programs for interneuron development.

Area of Science:

• Neuroscience
• Developmental Biology
• Genetics

Background:

• Neurodevelopmental disorders, including autism and schizophrenia, are linked to alterations in specific neuronal populations.
• Cortical and striatal gamma-aminobutyric acid–expressing (GABAergic) neurons are particularly implicated in these conditions.
• Understanding the early development of these neurons is critical for deciphering disease mechanisms.

Purpose of the Study:

• To characterize the cellular diversity and developmental trajectories of GABAergic neurons in the human fetal brain.
• To investigate the transcriptional programs governing the specification and differentiation of these neurons.
• To compare human GABAergic neuron development with established rodent models.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) was employed to analyze cell populations in human ganglionic eminences.
• scRNA-seq data was used to identify regional and temporal diversity among progenitor cells.
• Computational analysis was performed to infer transcriptional regulatory logic.

Main Results:

• Identified significant regional and temporal diversity within progenitor cells of the human ganglionic eminences.
• Characterized the emergence of diverse projection neurons and interneurons.
• Found that transcriptional programs for GABAergic neuron specification in humans are similar to those in rodents.
• Revealed conserved regulatory mechanisms controlling GABAergic neuron development in the human telencephalon.

Conclusions:

• The human ganglionic eminences exhibit complex progenitor cell diversity crucial for generating various GABAergic neuron types.
• The developmental pathways for human GABAergic neurons share conserved regulatory logic with rodents.
• These findings provide insights into the evolutionary basis of human brain development and neurodevelopmental disorders.