# Development of the blood–brain barrier

## TL;DR

This review explains how the blood-brain barrier forms during brain development and the key factors involved in its creation.

## Contribution

The paper provides a comprehensive summary of the cellular and molecular mechanisms underlying blood-brain barrier development.

## Key findings

- The blood-brain barrier develops alongside the central nervous system's vasculature.
- The Wnt/β-catenin signaling pathway is crucial for the initial formation of the blood-brain barrier.
- Multiple cell types collaborate in orchestrating blood-brain barrier development.

## Abstract

The blood–brain barrier (BBB) is a term used to describe the specialized properties of vasculature in the central nervous system (CNS) that regulate the exchange of ions, molecules and cells, thereby maintaining CNS homeostasis. These BBB properties are largely possessed by vascular endothelial cells, which exhibit molecular specializations that distinguish them from endothelial cells in other organs. BBB development – orchestrated by complex interactions between endothelial cells, neural progenitor cells, pericytes, astrocytes, neurons and other cell types that form the neurovascular unit – is initiated concurrently with CNS angiogenesis and continues during expansion and maturation of the vasculature. Importantly, the Wnt/β-catenin signaling pathway plays a central role in barriergenesis, the initial acquisition of BBB phenotype in endothelial cells. In this Review, we summarize current understanding of BBB development, including timing and underlying cellular and molecular mechanisms. We also discuss established and emerging techniques for studying BBB development and highlight important unanswered questions in the field.

Summary: A Review of the development of the blood–brain barrier, including timing, underlying cellular and molecular mechanisms, established and emerging tools and techniques, and important unanswered questions.