The Spatial and Temporal Origin of Chandelier Cells in Mouse Neocortex

Building Cross Connectivity Chandelier cells innervate the initial segment of axons from pyramidal neurons and are thus placed to regulate pyramidal cell circuits in the brain. Chandelier cells of mice are marked by expression of the NKX2.1 transcription factor. Taniguchi et al. (p. 70, published online 22 November) followed the development of these neurons and found that chandelier cells originate from the ventral germinal zone. The nascent cells migrate and integrate with cortical neurons following specific developmental pathways. Chandelier interneurons migrate along well-defined paths as they mingle with pyramidal neurons to build circuits. Diverse γ-aminobutyric acid–releasing interneurons regulate the functional organization of cortical circuits and derive from multiple embryonic sources. It remains unclear to what extent embryonic origin influences interneuron specification and cortical integration because of difficulties in tracking defined cell types. Here, we followed the developmental trajectory of chandelier cells (ChCs), the most distinct interneurons that innervate the axon initial segment of pyramidal neurons and control action potential initiation. ChCs mainly derive from the ventral germinal zone of the lateral ventricle during late gestation and require the homeodomain protein Nkx2.1 for their specification. They migrate with stereotyped routes and schedule and achieve specific laminar distribution in the cortex. The developmental specification of this bona fide interneuron type likely contributes to the assembly of a cortical circuit motif.