Mechanisms regulating area-specific interneuron distributions in the cerebral cortex

The cerebral cortex depends on a precise balance of excitatory pyramidal cells (PCs) and inhibitory interneurons (INs), but how IN distributions specific to different areas develop remains unknown. Contrary to the idea that programmed cell death shapes these patterns after birth, preliminary data suggest that INs are heterogeneously deployed before programmed cell death through yet-to-be-identified molecular cues. The IN-PATTERNS project proposes that a global molecular code, mainly driven by signals from PCs, guides different IN allocations across cortical areas. To test this hypothesis, this project combines (i) single-cell RNA sequencing and bioinformatic ligand–receptor analyses to build a comprehensive PC–IN interactome when interneurons stop migrating; (ii) high-resolution spatial transcriptomics to map candidate gene expression; and (iii) in utero electroporation to causally validate PC cues. This interdisciplinary approach will provide public datasets, molecular atlases, and open-source analysis tools, forming a basis for understanding cortical circuit assembly and its disruption in disease. With the expertise of the Marin lab in interneuron biology and genomics, along with dedicated support from the Centre's bioinformatics team and my experience in mouse embryology, IN-PATTERNS is ambitious but feasible, with the potential to significantly advance my training and establish new paradigms in developmental neuroscience.