Regulation of Neurogenesis in Mouse Brain by HMGB1

• Published in: Cells (Basel, Switzerland) Vol. 9; no. 7; p. 1714
• Main Authors: Zhao, Xiang, Rouhiainen, Ari, Li, Zhilin, Guo, Su, Rauvala, Heikki
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 17.07.2020; MDPI
• Subjects: Animals; Apoptosis; Axonogenesis; Brain; Brain - growth & development; Brain - metabolism; brain development; Cell adhesion & migration; Cell cycle; Cell differentiation; Cell Proliferation; Cells, Cultured; Central nervous system; Chemokine CXCL12 - metabolism; CXCL12; CXCL12 protein; CXCR4; CXCR4 protein; differentiation; Down-Regulation; Embryo, Mammalian - metabolism; Embryos; Forebrain; Foxg1 protein; Gene regulation; High mobility group proteins; HMGB1; HMGB1 protein; HMGB1 Protein - metabolism; Immune system; Inflammation; Invertebrates; Laboratory animals; Mice, Inbred C57BL; Mice, Knockout; Morphogenesis; Nervous system; Neural stem cells; Neural Stem Cells - metabolism; Neurogenesis; Neurons - metabolism; Progenitor cells; Proteins; Receptors, CXCR4 - metabolism; Rodents; Stem cell transplantation; Transcription factors; Transcription Factors - metabolism; Wnt protein; β-Catenin; United States > US; Switzerland; Germany; brain development; neurogenesis; CXCR4; CXCL12; differentiation; HMGB1
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells9071714

The High Mobility Group Box 1 (HMGB1) is the most abundant nuclear nonhistone protein that is involved in transcription regulation. In addition, HMGB1 has previously been found as an extracellularly acting protein enhancing neurite outgrowth in cultured neurons. Although HMGB1 is widely expressed in the developing central nervous system of vertebrates and invertebrates, its function in the developing mouse brain is poorly understood. Here, we have analyzed developmental defects of the HMGB1 null mouse forebrain, and further examined our findings in ex vivo brain cell cultures. We find that HMGB1 is required for the proliferation and differentiation of neuronal stem cells/progenitor cells. Enhanced apoptosis is also found in the neuronal cells lacking HMGB1. Moreover, HMGB1 depletion disrupts Wnt/β-catenin signaling and the expression of transcription factors in the developing cortex, including Foxg1, Tbr2, Emx2, and Lhx6. Finally, HMGB1 null mice display aberrant expression of CXCL12/CXCR4 and reduced RAGE signaling. In conclusion, HMGB1 plays a critical role in mammalian neurogenesis and brain development.