Genes & diseasesAug 20, 2026

CCN1 may control microglia placement by region-specific cell interactions

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Aug 21, 2026

Abstract

CCN1 deletion in neural stem cells resulted in a significant reduction of microglia in the ventricular zone at E17.5 and P2.

Microglia showed increased aggregation and activation specifically in the rostral lateral septum following CCN1 deletion.
Significant expression changes in autophagy- and activation-related genes were observed in CCN1-deficient mice.
Dysregulation of key signaling ligands Csf1 and Il2 occurred in a region-specific manner due to CCN1 deletion.
Elevated levels of Csf1 and Il2 were noted specifically in the LSR region, affecting the status of microglia there.
The findings indicate a complex interaction between neural stem cells and microglia regulated by CCN1 during brain development.

Simplified

During brain development, neural stem progenitor cells (NSPCs) and microglia interact within precise spatial niches; however, decoding mechanism is full of challenges using traditional analytical techniques. Here, we investigated the role of CCN1, a secreted protein enriched in NSPCs, using CNS-specific Ccn1 knockout mice. Through single cell RNA-seq analysis, we found that microglia were significantly reduced in the ventricular zone (VZ) at E17.5 and P2, with elevated expression of autophagy- and activation-related genes in Ccn1-CKO mice. Spatial transcriptomics at P2 further showed that Ccn1 deletion region-specific redistributes microglia and leads to increased microglial aggregation and activation in the rostral lateral septum (LSR), alongside reductions in the VZ. Mechanistically, Ccn1 deletion in NSCs led to region-specific dysregulation of the key signaling ligands, Csf1 and Il2. We found the elevated expression of Csf1 and Il2 specifically within the LSR region, which corresponded to the up-regulation of their respective receptors (Csf1r, Cd53) and downstream targets (Spp1, Ctsb) in LSR microglia, affecting microglial status. Our study reveals a region-specific NSC-microglia interaction regulated by Ccn1, offering a new paradigm for understanding multicellular dynamics in brain development.

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CCN1 may control microglia placement by region-specific cell interactions

Abstract

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