Rbfox1 mediates cell-type specific splicing in cortical interneurons

Cortical interneurons display a remarkable diversity in their morphology, physiological properties and connectivity. Elucidating the molecular determinants underlying this heterogeneity is essential for understanding interneuron development and function. We discovered that alternative splicing differentially regulates the integration of somatostatin- and parvalbumin-expressing interneurons into nascent cortical circuits through the cell-type specific tailoring of mRNAs. Specifically, we identified a role for the activity-dependent splicing regulator Rbfox1 in the development of cortical interneuron subtype specific efferent connectivity. Our work demonstrates that Rbfox1 mediates largely non-overlapping alternative splicing programs within two distinct but related classes of interneurons. Overall design: RNA-seq of FACS sorted PV+ and SST+ cortical interneuronals at P8 of wt and conditional Rbfox1 Kos皮层中间神经元（cortical interneurons）在形态学、生理特性及连接特性上展现出显著的多样性。阐明该异质性背后的分子决定因素，对于理解中间神经元的发育与功能至关重要。本研究发现，可变剪接（alternative splicing）通过对信使RNA（messenger RNA）进行细胞类型特异性的精准调控，差异性介导表达生长抑素（somatostatin）与小白蛋白（parvalbumin）的中间神经元向新生皮层环路的整合过程。具体而言，我们明确了活性依赖型剪接调控因子（activity-dependent splicing regulator）Rbfox1在皮层中间神经元亚型特异性传出连接（efferent connectivity）发育过程中的关键作用。本研究证实，Rbfox1在两类截然不同但又紧密相关的中间神经元群体中，介导了几乎完全非重叠的可变剪接程序。实验整体设计：对野生型（wild type）与条件性Rbfox1敲除（conditional Rbfox1 knockout）小鼠在出生后第8天（P8）经荧光激活细胞分选（fluorescence-activated cell sorting, FACS）获取的PV阳性与SST阳性皮层中间神经元进行RNA测序（RNA-seq）。