High Mobility Group Box-1 (HMGB1; Amphoterin) Is Required for Zebrafish Brain Development

• Published in: The Journal of biological chemistry 2011-07, Vol.286 (26), p.23200-23213
• Main Authors: Zhao, Xiang, Kuja-Panula, Juha, Rouhiainen, Ari, Chen, Yu-chia, Panula, Pertti, Rauvala, Heikki
• Format: Article
• Language: English
• Subjects: Animals; Brain; Cell Proliferation - drug effects; Cell Surface Protein; Cell Survival - drug effects; Cell Survival - physiology; Cell Survival and Proliferation; Cellular Regulation; Development; Dopaminergic Neurons; Gene Expression Regulation, Developmental - drug effects; Gene Expression Regulation, Developmental - physiology; HMGB1 Protein - biosynthesis; HMGB1 Protein - genetics; Nerve Tissue Proteins - biosynthesis; Nerve Tissue Proteins - genetics; Neural Progenitors; Neural Stem Cells - cytology; Neural Stem Cells - metabolism; Neurobiology; Neuroscience; Oligodeoxyribonucleotides, Antisense - pharmacology; Prosencephalon - cytology; Prosencephalon - embryology; Zebra Fish; Zebrafish - embryology; Zebrafish - genetics; Zebrafish Proteins - biosynthesis; Zebrafish Proteins - genetics
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M111.223834

Hmgb1 (high mobility group box-1; amphoterin) is highly expressed in brain during early development of vertebrate and nonvertebrate species. However, its role in brain development remains elusive. Here we have cloned the zebrafish Hmgb1 and specifically manipulated Hmgb1 expression using injection of morpholino antisense oligonucleotides or Hmgb1 cRNA. The HMGB1 knockdown morphants produced by injection of three different morpholino oligonucleotides display a characteristic phenotype with smaller size, smaller brain width, and shorter distance between the eyes. Closer examination of the phenotype reveals severe defects in the development of the forebrain that largely lacks catecholaminergic neural networks. The HMGB1 morphant is deficient in survival and proliferation of neural progenitors and displays fewer cell groups expressing the transcription factor Pax6a in the forebrain and aberrant Wnt8 signaling. The mechanism of HMGB1-dependent progenitor survival involves the neuronal transmembrane protein AMIGO (amphoterin-induced gene and orf), the expression of which is regulated by HMGB1 in vivo. Our data demonstrate that HMGB1 is a critical factor for brain development, enabling survival and proliferation of neural progenitors that will form the forebrain structures.