Center for Neurogenetics, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA; Weill Cornell/Rockefeller/Sloan Kettering Tri-Institutional MD-PhD Program, New York, NY 10021, USA.
Center for Neurogenetics, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA.
Cell Rep. 2024 Aug 27;43(8):114531. doi: 10.1016/j.celrep.2024.114531. Epub 2024 Jul 25.
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.
自发性和感觉诱发活动塑造发育中的回路。然而,这些活动模式如何与调节神经元亚型分化的细胞程序相交织,目前还不是很清楚。通过电生理和体内纵向分析,我们发现 C-X-C 基序趋化因子配体 14(Cxcl14),先前因其与肿瘤侵袭的关联而被表征的基因,在发育过程中表达于感觉皮层 I 层(LI)中的单花束细胞(SBC)中。新生儿期的感觉剥夺显著降低了 Cxcl14 的表达。此外,我们报告说,该基因的功能丧失会导致 SBC 的内在兴奋性增加,但不会增加 LI 神经胶质样细胞的兴奋性,并增强神经元的复杂性。此外,Cxcl14 的缺失会损害感觉图的形成,并损害感觉输入对浅层中间神经元的体内募集。这些结果表明 Cxcl14 是 LI 分化所必需的,并证明趋化因子作为皮质网络发育关键因素的新兴作用。