The cytokine receptor Fn14 regulates neuronal transcription during development and brain function in the adult [ATAC-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: ATACseq on Fn14 KO and WT mice or WT mice depleated of microglia and control mice.