Cell type composition and circuit organization of neocortical radial clones

Excitatory neurons arising from a common progenitor establish radially-oriented clonal units in the neocortex which have been proposed to serve as elementary information processing modules. To characterize the cell types and circuit diagram within these clonal units, we performed single-cell RNA-sequencing and multi-cell patch clamp recordings of neurons derived from Nestin-positive progenitors. We found that radial clones do not appear to be fate-restricted, but instead individual clones are composed of a random sampling of the transcriptomic cell types present in a particular cortical area. The effect of lineage on synaptic connectivity depends on the type of connection tested: pairs of clonally related neurons were more likely to be connected vertically, across cortical layers, but not laterally within the same layer, compared to unrelated pairs. We propose that integration of vertical input from related neurons with lateral input from unrelated neurons may represent a developmentally programmed motif for assembling neocortical circuits. Overall design: Electrophysiological measurements were performed on clonal neurons from a common progenitor spanning multiple brain layers and sampled across a multitude of regions in the mouse brain. mRNA was extracted from the same cells and made into sequence ready libraries using the Patch-seq/ Smart-Seq2 library preparation method