8/9 This atlas not only corroborated known interactions but also enabled the discovery of novel regulators, identifying 2 cadherin superfamily members as key mediators of perisomatic inhibition in deep vs superficial layer excitatory neurons by parvalbumin-expressing basket cells

7/9 Our LR atlas validated key interactions like CBLN4, which drives inhibitory synapse formation on GlutNs. It showed that CBLN4 exp is specific to Sst|L2/3-L5 fan-MCs, and predicted NEO1 as its primary receptor in the cortex. Proximity ligation assays confirmed this prediction

5/9 While neuron-pair specific LRs were rare, most LRs were shared by a relatively small subset of possible neuron-pairs (<100 out of 729 cell pairs). Ultimately, specificity arose from the unique combinations of these LRs per neuron-pair.

4/9 We then built an atlas predicting LR-mediated neuron-neuron interactions during cortical dev. It integrates the exp of ~8K LRs with downstream transcriptional networks across 729 neuronal pairs, prioritizing LR interactions based on known connectivity and neuronal maturation.

3/9 Using our extensive mammalian LR database (~8K pairs), we identified strong spatiotemporal correlations between ligands and receptors, suggesting their roles in neuronal interactions.

2/9 First, we tracked gene expression dynamics across 17 stages of mouse cortical development using our own and published data. This allowed us to generate “transcriptional landscapes,” capturing the spatiotemporal expression patterns of each major cortical neuron subtype.

1/9 The laminar organization and connectivity patterns among cortical neuronal subtypes exhibit remarkable specificity and stereotypy, but the molecular mechanisms orchestrating these phenomena remain enigmatic. We used sc and snRNA-seq to investigate these mechanisms in mice.

Delighted to showcase our atlas for the inference of ligand-receptor mediated interactions between neuronal subtypes during mouse cortex development. Herculean endeavor by former PhD student Rémi Mathieu (now @alleninstitute.bsky.social) and team, in collaboration with
@LudovicTelley

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