Nature neuroscience
July 1, 2025
Ya'El Courtney, Joshua P Head, Neil Dani et al.
10 citations
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.
bioRxiv : the preprint server for biology
January 16, 2024
Ya'El Courtney, Joshua P Head, Elizabeth D Yimer et al.
9 citations
preprint
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.
bioRxiv : the preprint server for biology
September 30, 2025
Ya'El Courtney, Josephine M Anderson, Christian Lagares-Linares et al.
preprint
In mice, the psychedelic drug LSD crosses the placenta and enters embryonic cerebrospinal fluid within minutes. A single dose during pregnancy alters the organization of the cerebral cortex in the offspring, and repeated doses shift the balance of neuron types and increase microglia. Adult offspring, especially males, show reduced prepulse inhibition and rotational stereotypy. These findings identify a mechanism by which maternal psychedelic exposure can lead to lasting changes in brain development and behavior.