# Akhirin Functions as an Innate Immune Barrier to Preserve Neurogenic Niche Homeostasis During Mouse Brain Development

## TL;DR

A protein called Akhirin protects the developing brain by preventing inflammation and keeping stem cells healthy.

## Contribution

This study identifies Akhirin as a novel innate immune barrier molecule in the developing neurogenic niche.

## Key findings

- AKH is secreted by choroid plexus epithelial cells and localizes to the ventricular surface during embryonic brain development.
- Loss of AKH increases inflammatory cytokines in cerebrospinal fluid and disrupts neural stem cell niche homeostasis.
- AKH's LCCL domain binds bacteria, offering innate immune protection in the neurogenic niche.

## Abstract

Akhirin (AKH) is secreted by choroid plexus epithelial cells and localizes to the ventricular surface during embryonic brain development.

Loss of AKH disrupts neural stem cell homeostasis by inducing inflammatory cytokines in the cerebrospinal fluid.

AKH is cleaved under inflammatory conditions, and its LCCL domain directly binds bacteria, providing innate immune protection in the developing neurogenic niche.

AKH functions as a barrier molecule that integrates immune defense with the maintenance of neural stem cell niche integrity during early neurodevelopment.

Neurogenesis is tightly regulated by complex interactions among neural stem and progenitor cells (NSCs/NPCs), blood vessels, microglia, and extracellular matrix components within the neurogenic niche. In the embryonic brain, NSCs reside along the ventricular surface, where cerebrospinal fluid (CSF) directly regulates their proliferation. Here, we identify Akhirin (AKH) as a critical regulator that preserves the integrity of the NSC niche during mouse brain development. At embryonic day 14.5, AKH is secreted and enriched at the apical surface of choroid plexus epithelial cells and the ventricular lining. Loss of AKH leads to increases the inflammatory cytokine expression in the CSF and disrupts NSC niche homeostasis. Furthermore, AKH is cleaved upon inflammatory stimulation, and its LCCL domain directly binds bacteria, thereby preventing their spread. These findings reveal that AKH functions as a protective barrier molecule within the developing neurogenic niche, providing immune protection and preserving NSC niche homeostasis during periods when the innate immune defenses are still immature.