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Cerebrospinal Fluid

Cerebrospinal Fluid

Cerebrospinal fluid (CSF) is a colorless liquid that flows around the brain and the spinal cord, playing a vital role in the protection, support, and overall function of the central nervous system (CNS). CSF production, circulation, and absorption are tightly regulated processes essential for the brain and spinal cord to function properly.
CSF Production
CSF is produced mainly in the choroid plexus, a network of capillaries and ependymal cells located within the ventricular system of the brain....

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Choroid plexus apocrine secretion shapes CSF proteome during mouse brain development.

Ya'el Courtney^1,2, Joshua P Head¹, Neil Dani^1,3

¹Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.

Nature Neuroscience

|May 28, 2025

Summary

This summary is machine-generated.

Embryonic choroid plexus (ChP) uses apocrine secretion to regulate cerebrospinal fluid (CSF) composition, influencing brain development. This pathway, when disrupted, can negatively impact neural progenitor dynamics and offspring behavior.

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Area of Science:

Neuroscience
Developmental Biology
Cell Biology

Background:

The choroid plexus (ChP) is crucial for regulating cerebrospinal fluid (CSF) composition and providing molecular cues for brain development.
Embryonic ChP secretory mechanisms are not well understood, particularly their role in neurodevelopment.

Purpose of the Study:

To identify the mechanisms of embryonic choroid plexus secretion.
To investigate the role of these secretions in regulating the CSF proteome and neurodevelopment.
To understand the impact of ChP secretion disruption on brain development and behavior.

Main Methods:

Activation of serotonergic 5-HT2C receptors using WAY-161503 to trigger Ca2+ signaling and apocrine secretion in mouse and human ChP.
Analysis of CSF proteome alterations.
In utero induction of ChP secretion in mice.
Assessment of neural progenitor dynamics, cerebral cortical architecture, and offspring behavior.
Investigation of ChP secretion in response to in-utero illness or drug exposure.

Main Results:

Apocrine secretion by embryonic ChP epithelial cells was identified as a key regulator of the CSF proteome and neurodevelopment.
Activation of 5-HT2C receptors by WAY-161503 induced sustained Ca2+ signaling and high-volume apocrine secretion.
ChP secretion altered the CSF proteome, stimulated neural progenitors, and shifted their developmental trajectory.
In utero induction of ChP secretion disrupted neural progenitor dynamics, cortical architecture, and offspring behavior.
Pregnancy-related illness or drug exposure (LSD) provoked coordinated embryonic ChP secretion.

Conclusions:

A fundamental apocrine secretory pathway in the embryonic choroid plexus shapes brain development.
Disruption of this pathway has significant and lasting consequences for neural progenitor dynamics, brain structure, and behavior.
This pathway represents a critical target for understanding and potentially intervening in neurodevelopmental disorders.