Esr1-Dependent Signaling and Transcriptional Maturation in the Medial Preoptic Area of the Hypothalamus Shapes the Development of Mating Behavior during Adolescence

• DOI: 10.7554/elife.106347.1
• Publication Date: 2025-05-01T14:30:14Z
• Authors: Koichi Hashikawa; Yoshiko Hashikawa; Brandy Briones; Kentaro Ishii; Yuejia Liu; Mark A Rossi; Marcus L Basiri; Jane Y Chen; Omar R Ahmad; Rishi V Mukundan; Nathan L Johnston; Rhiana C Simon; James C Soetedjo; Jason R Siputro; Jenna A McHenry; Richard D Palmiter; David R Rubinow; Larry S Zweifel; Garret D Stuber
• Keywords: Preoptic area

Mating and other behaviors emerge during adolescence through the coordinated actions of steroid hormone signaling throughout nervous system periphery. In this study, we investigated transcriptional dynamics medial preoptic area (MPOA), a critical region for reproductive behavior, using single-cell RNA sequencing (scRNAseq) in situ hybridization techniques male female mice development. Our findings reveal that estrogen receptor 1 (Esr1) plays pivotal role maturation GABAergic neurons within MPOA adolescence. Deletion gene, Esr1 , (Vgat+) disrupted developmental progression mating both sexes, while its deletion glutamatergic (Vglut2+) had no observable effect. males females, these displayed distinct trajectories, with hormone-dependent gene expression patterns emerging regulated by . neurons, prior to adolescence, arrested adolescent cells uncovered sex-specific gene-regulatory networks associated signaling. results underscore orchestrating revealing regulatory implicated development hypothalamic controlled behaviors.