HMGB1/CXCL12 heterocomplex activates CXCR4 to suppress the ability of Muller glia to become proliferating progenitor-like cells in the chick retina

HMGB1/CXCL12 heterocomplex signaling through CXCR4 limits Muller glia reprogramming into proliferating progenitor-like cells in the damaged chick retina.

• Why it matters: Injury-induced HMGB1 and CXCL12 signaling could shape whether Muller glia become MGPCs, but the pathway controlling this reactivity-to-reprogramming switch was unclear.
• What they did: In chick retinas, CXCR4 agonist or recombinant HMGB1/CXCL12 activated mTOR and Jak/Stat in Muller glia, while blocking CXCR4 signaling, HMGB1 nuclear export, or heterocomplex formation increased MGPC proliferation.
• The result: CXCR4 blockade potently stimulated MGPC proliferation without changing neuronal death or microglial activation, and HMGB1/CXCL12-CXCR4 inhibition failed to restore proliferation in microglia-depleted retinas.

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