Glia Cells Control Olfactory Neurogenesis by Fine-Tuning CXCL12

Author:

Dietz André1ORCID,Senf Katja1,Karius Julia1,Stumm Ralf1,Neuhaus Eva Maria1ORCID

Affiliation:

1. Pharmacology and Toxicology, Jena University Hospital, Friedrich Schiller University Jena, Drackendorfer Str. 1, 07747 Jena, Germany

Abstract

Olfaction depends on lifelong production of sensory neurons from CXCR4 expressing neurogenic stem cells. Signaling by CXCR4 depends on the concentration of CXCL12, CXCR4’s principal ligand. Here, we use several genetic models to investigate how regulation of CXCL12 in the olfactory stem cell niche adjusts neurogenesis. We identify subepithelial tissue and sustentacular cells, the olfactory glia, as main CXCL12 sources. Lamina propria-derived CXCL12 accumulates on quiescent gliogenic stem cells via heparan sulfate. Additionally, CXCL12 is secreted within the olfactory epithelium by sustentacular cells. Both sustentacular-cell-derived and lamina propria-derived CXCL12 are required for CXCR4 activation. ACKR3, a high-affinity CXCL12 scavenger, is expressed by mature glial cells and titrates CXCL12. The accurate adjustment of CXCL12 by ACKR3 is critical for CXCR4-dependent proliferation of neuronal stem cells and for proper lineage progression. Overall, these findings establish precise regulation of CXCL12 by glia cells as a prerequisite for CXCR4-dependent neurogenesis and identify ACKR3 as a scavenger influencing tissue homeostasis beyond embryonic development.

Funder

Deutsche Forschungsgemeinschaft

Publisher

MDPI AG

Subject

General Medicine

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