The choroid plexus (ChP) regulates cerebrospinal fluid (CSF) composition, providing essential molecular cues for brain development. Apocrine secretion by embryonic ChP epithelial cells is a key regulator of the CSF proteome and neurodevelopment in male and female mice. Activation of serotonergic 5-HT2C receptors triggers sustained calcium signaling, driving high-volume apocrine secretion in mouse and human ChP. This secretion alters the CSF proteome, stimulating neural progenitors and shifting their developmental trajectory. Inducing ChP secretion in utero disrupts neural progenitor dynamics, cerebral cortical architecture, and offspring behavior. Illness or lysergic acid diethylamide exposure during pregnancy provokes coordinated ChP secretion in mouse embryos. The findings reveal a fundamental secretory pathway in the ChP that shapes brain development, and its disruption can have lasting consequences for brain health.
Apocrine secretion by embryonic choroid plexus (ChP) epithelial cells contributes to the cerebrospinal fluid (CSF) proteome and influences brain development in mice. This process depends on sustained intracellular calcium signaling and calpain-mediated cytoskeletal remodeling, rapidly altering the CSF proteome and activating neural progenitors lining the brain's ventricles. Overactivation of this secretion—triggered by maternal administration of a serotonergic 5HT2C receptor agonist, maternal illness, or the psychedelic drug LSD during pregnancy—dysregulates cerebral cortical development, alters the fate of CSF-contacting neural progenitors, and changes adult social behaviors. These findings demonstrate a mechanism by which diverse maternal stressors disrupt in utero brain development.