A choroid plexus apocrine secretion mechanism shapes CSF proteome and embryonic brain development

Area of Science:

• Neuroscience
• Developmental Biology
• Cell Biology

Background:

• The embryonic choroid plexus (ChP) produces cerebrospinal fluid (CSF).
• The composition of embryonic CSF and its role in brain development are not fully understood.
• Cellular secretion mechanisms in the ChP are under investigation.

Purpose of the Study:

• To investigate the role of apocrine secretion by embryonic ChP cells in shaping the CSF proteome.
• To determine the signaling pathways involved in ChP apocrine secretion.
• To examine the impact of altered ChP secretion on embryonic brain development and adult behavior.

Main Methods:

• Utilized mouse models to study embryonic ChP secretion.
• Investigated intracellular calcium signaling and calpain activity.
• Administered maternal serotonergic 5HT2C receptor agonists, simulated maternal illness, and LSD during pregnancy.
• Assessed effects on embryonic CSF proteome, neural progenitor fate, cerebral cortical development, and adult social behaviors.

Main Results:

• Discovered apocrine secretion by embryonic ChP cells contributes to the CSF proteome.
• Identified sustained intracellular calcium signaling and calpain-mediated cytoskeletal remodeling as key mechanisms.
• Demonstrated that supraphysiological apocrine secretion dysregulates cerebral cortical development and alters neural progenitor fate.
• Showed that maternal exposure to stressors (illness, LSD) overactivates ChP secretion, impacting offspring development.

Conclusions:

• Apocrine secretion by embryonic ChP cells is a significant mechanism influencing the embryonic CSF proteome and brain development.
• Maternal exposure to specific drugs and stressors can lead to excessive ChP secretion, disrupting normal fetal brain development.
• This research reveals a novel pathway through which maternal factors impact neurodevelopment, with potential implications for understanding behavioral disorders.