Inferring Ligand-Receptor Interactions between GABAergic and Glutamatergic neurons during somatosensory cortex development

The cerebral cortex hosts a diverse array of excitatory and inhibitory neuron types, each characterized by distinct positional and synaptic connectivity patterns, yet the molecular mechanisms driving this stereotyped organization remain largely unknown. To identify ligand-receptor (LR) pairs that regulate interactions and connectivity between cortical neurons during embryonic and postnatal development, we tracked the transcriptional dynamics of all genes across all cortical neuron types at 17 time points spanning the entire course of cortical development. Using this data, we built a comprehensive bioinformatic atlas to infer significant LR-mediated interactions among all neuron types throughout cortical maturation. This atlas not only validated observations but also served as a powerful tool for hypothesis generation, revealing the critical role of two cadherin superfamily members in mediating perisomatic inhibition of deep and superficial layer excitatory neurons by neighboring parvalbumin-expressing basket cells.