A choroid plexus apocrine secretion mechanism shapes CSF proteome and embryonic brain development.
Ya'El Courtney, Joshua P Head, Elizabeth D Yimer, Neil Dani, Frederick B Shipley, Towia A Libermann, Maria K Lehtinen
bioRxiv : the preprint server for biology January 16, 2024 preprint DOI: 10.1101/2024.01.08.574486 via PubMed
Summary
AI-generated from the abstractApocrine 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.
Study at a glance
| Characteristics | Experimental study |
|---|---|
| Population | Mice |
| Interventions | serotonergic 5HT2C receptor agonist LSD |
| Keywords | Neuroscience Maternal health Fetal development Brain physiology Developmental biology |
| Citations | 9 |
| Key finding | Apocrine secretion by embryonic choroid plexus epithelial cells contributes to the CSF proteome and influences brain development, and its overactivation by maternal stressors such as a 5HT2C receptor agonist, illness, or LSD disrupts cortical development and adult social behaviors. |
Abstract
We discovered that apocrine secretion by embryonic choroid plexus (ChP) epithelial cells contributes to the cerebrospinal fluid (CSF) proteome and influences brain development in mice. The apocrine response relies on sustained intracellular calcium signaling and calpain-mediated cytoskeletal remodeling. It rapidly alters the embryonic CSF proteome, activating neural progenitors lining the brain's ventricles. Supraphysiological apocrine secretion induced during mouse development by maternal administration of a serotonergic 5HT2C receptor agonist dysregulates offspring cerebral cortical development, alters the fate of CSF-contacting neural progenitors, and ultimately changes adult social behaviors. Critically, exposure to maternal illness or to the psychedelic drug LSD during pregnancy also overactivates the ChP, inducing excessive secretion. Collectively, our findings demonstrate a new mechanism by which maternal exposure to diverse stressors disrupts in utero brain development.