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

Journal Article (2026)
Author(s)

Jari B. Berkhout (Leiden University Medical Center)

Sophie Trender (Heidelberg University Hospital)

Quirin Krabichler (Universität Heidelberg)

Yuval Podpecan (Heidelberg University Hospital)

Felix Franke (Heidelberg University Hospital)

Tim Schubert (Heidelberg University Hospital)

Peter Burbach ( University Medical Centre Utrecht)

Valery Grinevich (Universität Heidelberg)

Roger Adan ( University Medical Centre Utrecht)

Henning Fröhlich (Heidelberg University Hospital)

Ferdinand Althammer (Heidelberg University Hospital)

Onno C. Meijer (Leiden University Medical Center)

Ahmed Mahfouz (Leiden University Medical Center, TU Delft - Electrical Engineering, Mathematics and Computer Science)

Research Group
Pattern Recognition and Bioinformatics
DOI related publication
https://doi.org/10.1016/j.isci.2026.115604 Final published version
More Info
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Publication Year
2026
Language
English
Research Group
Pattern Recognition and Bioinformatics
Journal title
iScience
Issue number
5
Volume number
29
Article number
115604
Downloads counter
13
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Abstract

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.