The inner CSF-brain barrier: developmentally controlled access to the brain via intercellular junctions.

Area of Science:

• Neuroscience
• Developmental Biology
• Cell Biology

Background:

• The adult inner cerebrospinal fluid-brain barrier (CSF-BB) is formed by ependymal cells with gap junctions, allowing free diffusion.
• During development, neuroepithelial and radial glial cells form a barrier with "strap" junctions, restricting molecular exchange.

Purpose of the Study:

• To systematically investigate the developmental changes in the permeability of the inner CSF-BB in mice.
• To identify the molecular mechanisms underlying these permeability changes.

Main Methods:

• Permeability studies across the inner CSF-BB from embryonic day 17 (E17) to adulthood.
• Transcriptomic analysis of junctional proteins at the CSF-brain interface.
• Immunohistochemistry to localize specific junctional proteins.

Main Results:

• Fetal inner CSF-BB restricts exchange to small molecules (286 Da); this restriction is progressively lost during development.
• By postnatal day 20 (P20), molecules the size of plasma proteins (70 kDa) diffuse freely.
• Adherens junctional proteins (N-cadherin, β- and α-catenin) are present during development but decrease in adults, while gap junctions and claudin-11 appear in adults.

Conclusions:

• The inner CSF-BB undergoes significant developmental changes in permeability, transitioning from a restrictive barrier to a more permeable one.
• These permeability shifts are associated with dynamic changes in the expression and localization of junctional proteins, including adherens junctions, gap junctions, and claudins.
• Understanding these developmental changes is crucial for comprehending brain physiology and potential therapeutic interventions.