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The mammalian cerebral cortex is a complex laminar structure with a variety of neuronal and non-neuronal cell types that develop in a finely orchestrated and stereotypic manner. Final laminar position and synaptic specificity of most cortical cell types are well described. Strikingly, any alteration in the developmental unfolding of one of these processes, even for a single cell type among tens, can be sufficient to generate neurodevelopmental disorders. However, how the establishment of this precise cellular architecture is regulated at the molecular level remains largely unknown. Several lines of evidence suggest a role of cell-cell communications via ligand-receptor (LR) interactions. Using a single cell RNA-seq (scRNA-seq) approach in mice, we have generated a bioinformatic atlas that infers LR based cellular communications across all cell types over somatosensory (SS) cortex development. Querying our atlas for known LR interactions has demonstrated its validity, but new LR-mediated cell-cell interactions remain to be discovered to interrogate its power as a hypothesis generator. In parallel, a technique called Multiplexed-Error Robust Fluorescence In Situ Hybridization (MERFISH) has been recently developed and implemented by us, which images single cell transcriptomes in situ and thereby adds precious information about spatial expression. Here, we will: (i) test some LR interactions predicted by our scRNA-seq atlas for a role in SS microcircuit development, (ii) build on the MERFISH technique to complement our atlas with spatial information and to characterize SS cortex cellular development with unprecedented resolution and (iii) use MERFISH to interrogate altered developmental processes in the SS cortex of a mouse model of neurodevelopmental disorder, the Neurod2 KO mouse.
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