SOX2 and NR2F1 coordinate the gene expression program of the early postnatal visual thalamus

The thalamic dorsolateral geniculate nucleus (dLGN) receives visual input from the retina via the optic nerve, and projects to the cortical visual area, where eye-derived signals are elaborated. The transcription factors SOX2 and NR2F1 are directly involved in the differentiation of dLGN neurons, based on mouse work and patient mutations leading to vision defects. However, whether they regulate each other, or control common targets is still unclear. By RNA-seq analysis of neonatal dLGN from thalamo-specific Sox2 and Nr2f1 mouse mutants, we found a striking overlap of deregulated genes. Among them, Vgf, encoding a cytokine transported along thalamic-cortical axons is strongly downregulated in both mutants. Direct SOX2 binding to some of these genes was confirmed by CUT&RUN, which identified a SOX2 chromatin-binding pattern characteristic of the dLGN. Collectively, our genetic and molecular analyses on the SOX2 and NR2F1-coregulated genes contribute to our understanding of the gene regulatory network driving the differentiation and connectivity of thalamic neurons, and the vision impairments caused by mutations in these genes.