Combinatorial Cell-Adhesion and Activity Codes Instruct Cortical Modality Identity

The emergence of functional sensory modalities requires precise cortical arealization and thalamocortical connectivity. While early morphogen gradients broadly initiate cortical patterning, how sensory identity is specified and refined within these territories remains unclear. Using single-nucleus RNA sequencing and spatial transcriptomics, we reveal distinct modality-specific identity genes in primary somatosensory and visual cortices at early stages. These genes are enriched in thalamo-recipient layers and linked to neuronal activity and cell adhesion. Disrupting early thalamic activity alters both cortical activity and the expression of a subset of these genes, demonstrating a causal role for thalamic input in sensory modality acquisition. Remarkably, a core set of identity genes is already differentially expressed embryonically, before thalamic innervation, and encodes cell-adhesion profiles matching those of sensory thalamus, potentially enabling homophilic interactions. Our findings support a two-step model: cortical cell-adhesion codes prime modality-specific thalamocortical targeting, which is subsequently refined by patterned thalamic activity to establish functional cortical modalities.