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

📣 We’re hiring! 🚨 PhD position to study SOCIAL CODING in 🐭 S1 and mPFC using longitudinal INSCOPIX recordings from WT and socially amnesic mice during social tasks! Strong data analysis & computational modeling component. Co-sup with @lorifonto & @GuignardLab. DM if interested

Thrilled to share our work on how neural stem cells (NSCs) interact with distinct cell types in their niche. We use Ca2+ imaging in NSC processes and post-hoc iterative immunolabeling for multiple cell types to link NSCs functional activity to niche cell types inducing it. 1/8

Exciting developments ahead in LR predictions with developmental spatial transcriptomics and a focus on non-neuronal cells !!!!

All that, and more! Big thanks to X-less Rémi Mathieu and @LudovicTelley who made everything go !!!! And the other collaborators of course Thanks to the funding bodies: @EU_H2020, @FRM_officiel, @AgenceRecherche, @Inserm, @FondLejeune, @frcneurodon, @Rotary

9/9 These findings underscore the power of large-scale transcriptional profiling to unravel fundamental molecular mechanisms driving cortical circuit assembly.

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

6/9 LRs linked to autism and epilepsy were widely used in the somatosensory cortex (examined here), while LRs linked to schizophrenia and intellectual disabilities may affect interactions beyond this area.

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.

https://t.co/GsotIchWPk

#postdoc and #phdposition available in my lab in Marseille @centuri_ls & @inmed_u1249 🎉🎉 If you are interested in building models of brain computations and developing data analysis tools with cool experimental collaborators, please apply! More info: https://t.co/6tc4MKMufo

https://t.co/o7M2oSnBSG Increased activity of BHLHE22, FOXG1, EOMES, and NEUROD2 in organoids from macrocephalic ASD, the opposite for normocephalic ASD

Job alert 📢 We have an open position for a bioinformatician (post-doc or PhD student/engineer) to analyze spatial transcriptomics data & uncover ligand-receptor interactions regulating dev & connectivity of the mouse cerebral cortex. 🙏 RT More info https://t.co/nWtUmlI2ea

📣 Job alert!📍 We have an opening PhD position to study the role of local interneurons in flexible or stereotyped motor behavior. DM me if you want to join us in sunny Marseille!!

Huge congrats Rosa, well deserved !!!!