Choroid plexus apocrine secretion shapes CSF proteome during mouse brain development

The choroid plexus (ChP) regulates cerebrospinal fluid (CSF) composition, providing essential molecular cues for brain development; yet, embryonic ChP secretory mechanisms remain poorly defined. Here we identify apocrine secretion by embryonic ChP epithelial cells as a key regulator of the CSF proteome and neurodevelopment in male and female mice. We demonstrate that the activation of serotonergic 5-HT_2C receptors (by WAY-161503) triggers sustained Ca²⁺ signaling, driving high-volume apocrine secretion in mouse and human ChP. This secretion alters the CSF proteome, stimulating neural progenitors lining the brain's ventricles and shifting their developmental trajectory. Inducing ChP secretion in utero in mice disrupts neural progenitor dynamics, cerebral cortical architecture and offspring behavior. Additionally, illness or lysergic acid diethylamide exposure during pregnancy provokes coordinated ChP secretion in the mouse embryo. Our findings reveal a fundamental secretory pathway in the ChP that shapes brain development, highlighting how its disruption can have lasting consequences for brain health.