The chemokine Cxcl14 regulates interneuron differentiation in layer I of the somatosensory cortex

Spontaneous and sensory-evoked activity sculpts developing circuits. Yet, how these activity patterns intersect with cellular programs regulating the differentiation of neuronal subtypes is not well understood. Through electrophysiological and in vivo longitudinal analyses, we show that C-X-C motif chemokine ligand 14 (Cxcl14), a gene previously characterized for its association with tumor invasion, is expressed by single-bouquet cells (SBCs) in layer I (LI) of the somatosensory cortex during development. Sensory deprivation at neonatal stages markedly decreases Cxcl14 expression. Additionally, we report that loss of function of this gene leads to increased intrinsic excitability of SBCs—but not LI neurogliaform cells—and augments neuronal complexity. Furthermore, Cxcl14 loss impairs sensory map formation and compromises the in vivo recruitment of superficial interneurons by sensory inputs. These results indicate that Cxcl14 is required for LI differentiation and demonstrate the emergent role of chemokines as key players in cortical network development. [Display omitted] •Activity-dependent Cxcl14 expression delineates developing SBCs in layer I (LI)•Loss of Cxcl14 causes increased intrinsic excitability and neuronal complexity•5HT3aR.Cxcl14fl/fl mice show abnormal barrel map formation•LI interneurons show decreased network activity in 5HT3aR.Cxcl14fl/fl mice Iannone et al. characterize the development of single-bouquet cells (SBCs) and neurogliaform cells (NGFCs) in LI. They show that Cxcl14 expression in SBCs is crucial for morphological and electrophysiological maturation. In addition, loss of Cxcl14 impairs sensory-evoked responses in LI and the proper development of the barrel map in LIV.