Lineage Relationships Do Not Drive MGE/PoA-Derived Interneuron Clustering in the Brain

Neocortical excitatory and inhibitory neurons derive from distinct progenitor domains during embryonic development and migrate to their final positions, where they assemble into functional circuits. This process appears to be influenced by lineage relationships among locally born excitatory neurons, raising the intriguing possibility that this might be true for cortical interneurons. Two recent articles by the Fishell laboratory and our own used retrovirus-encoded DNA barcodes as unambiguous lineage-tracing tools to address this question, finding that clonally related inhibitory interneurons dispersed widely across the forebrain (Harwell et al., 2015; Mayer et al., 2015). This Matters Arising Response addresses the Sultan et al. (2016) Matters Arising paper, published concurrently in Neuron, where the authors reanalyze the datasets from both studies and propose a new interpretation, whereby clonally related interneurons would be considered clustered according to specific spatial constraints. After studying the report from Sultan et al. (2016) and carefully revisiting previously published studies, we find no evidence of lineage-dependent MGE/PoA-derived interneuron clustering in the forebrain.