The cytokine receptor Fn14 regulates neuronal transcription during development and brain function in the adult [RNA-seq]

Signaling between the cytokine TWEAK and its receptor Fn14 is critical for neural circuit development in the postnatal brain. However, the downstream mechanisms through which TWEAK and Fn14 mediate synapse development have remained unclear. Here, we apply single-nucleus RNA-sequencing to Fn14 and TWEAK KO mice to characterize the genes that are regulated by this pathway in the developing dorsal lateral geniculate nucleus of the thalamus at single-cell resolution. We identify robust cohorts of genes that are misregulated in the absence of either Fn14 or TWEAK, providing insight into the transcriptional mechanisms through which cytokine signaling between microglia and neurons regulates a key phase of postnatal brain development that is driven by sensory experience. Overall design: We performed single-nucleus RNA-sequencing using the inDrops approach on the dorsal lateral geniculate nuclei (dLGNs) of Fn14 and TWEAK knockout mice and their respective wild type littermates. Two biological replicates were included in the Fn14 dataset and four biological repliates were included in the TWEAK dataset.