FOXP1 is differentially active during development of murine vasopressin and oxytocin magnocellular neurons

Hypothalamic arginine vasopressin (AVP) and oxytocin (OXT) magnocellular neurons (MCNs), share a developmental lineage. The transcription factors driving specification are yet unknown. Using gene regulatory network analysis on published single-cell RNA-sequencing data of the developing mouse hypothalamus, we identified RORA, EBF3, FOXP1, FOXP2, and BCL11B as candidate transcription factors for differential MCN specification. We modeled developmental gene expression dynamics using computational cell fate mapping, revealing enrichment of EBF3 and BCL11B in the Avp lineage, and FOXP1 and FOXP2 in the Oxt lineage. In silico analysis of Avp and Oxt promoters predicted a binding site for FOXP1 and FOXP2, and an in vitro reporter assay identified regulation on both Avp and Oxt genomic promoters. Finally, heterozygous FOXP1 knockout mice exhibited a significant reduction in AVP and OXT neuron abundance, with OXT neurons disproportionally affected. We conclude that FOXP1 participates in MCN development, while being differentially active in OXT MCNs relative to AVP MCNs.