A TRANSCRIPTOMIC FRAMEWORK FOR INFERRING LIGAND–RECEPTOR INTERACTIONS DURING CORTICAL DEVELOPMENT

The assembly of cortical circuits relies on regulated molecular interactions between developing neuronal populations, yet the ligand–receptor (LR) logic governing these processes remains incompletely understood. To systematically infer LR-mediated cell–cell communication during cortical development, we integrated single-cell and single-nucleus RNA-seq data from the mouse somatosensory cortex across 17 developmental stages spanning embryonic to adult life. We generated a comprehensive transcriptomic dataset of cortical neurons by profiling key postnatal windows of circuit formation, including P0–P2 (radial migration and laminar allocation), P5–P8 (programmed cell death of glutamatergic and GABAergic neurons), and P16–P30 (synaptic refinement and circuit maturation). These data were combined with previously published embryonic (E11.5–E18.5) and adult datasets, including ganglionic eminence–derived populations, to capture early transcriptional programs of future cortical interneurons. By cross-referencing cell-type–resolved expression profiles with curated ligand–receptor databases, we inferred dynamic and stage-specific interaction networks across excitatory and inhibitory neuronal subtypes. This analysis revealed temporally restricted ligand–receptor pairs associated with neuronal migration, subtype specification, and synaptic wiring, highlighting context-dependent molecular programs underlying cortical circuit assembly. To facilitate exploration of these results, we developed an interactive Shiny application enabling users to query ligand–receptor interactions across developmental stages and neuronal populations. In parallel, we are extending this framework using spatial transcriptomics (MERFISH) to incorporate precise cellular positioning and enable spatially resolved inference of ligand–receptor interactions. Together, this work provides a comprehensive framework for investigating molecular communication underlying somatosensory cortical wiring and offers a publicly accessible resource for hypothesis generation.