Hippocampal CA1 Somatostatin Interneurons Originate in the Embryonic MGE/POA

Oriens lacunosum-moleculare (O-LM) interneurons constitute 40% of hippocampal interneurons expressing Somatostatin (SST). Recent evidence has indicated a dual origin for these cells in the medial and caudal ganglionic eminences (MGE and CGE), with expression of Htr3a as a distinguishing factor. This is strikingly different from cortical SST interneurons that have a single origin within the MGE/preoptic area (POA). We reassessed the origin of hippocampal SST interneurons using a range of genetic lineage-tracing mice combined with single-cell transcriptomic analysis. We find a common origin for all hippocampal SST interneurons in NKX2-1-expressing progenitors of the telencephalic neuroepithelium and an MGE/POA-like transcriptomic signature for all SST clusters. This suggests that functional heterogeneity within the SST CA1 population cannot be attributed to a differential MGE/CGE genetic origin. [Display omitted] •NKX2-1+ progenitors generate all hippocampal CA1 somatostatin (SST) interneurons•SST+ cells generated in the absence of NKX2-1 do not migrate to the hippocampus•LHX6 expression maintained in MGE-derived cortical and hippocampal CA1 interneurons•Low expression of Htr3a is detected in MGE-derived hippocampal CA1 interneurons In this article, Kessaris and colleagues combine genetic lineage tracing and single-cell transcriptomic analysis to identify the embryonic origin of hippocampal CA1 Somatostatin interneurons. They report a common origin in the medial ganglionic eminence/preoptic area from neuroepithelial precursors expressing NKX2-1.