PUBLICATION

High mobility group box-1 (HMGB1; amphoterin) is required for zebrafish brain development

Authors
Zhao, X., Kuja-Panula, J., Rouhiainen, A., Chen, Y.C., Panula, P., and Rauvala, H.
ID
ZDB-PUB-110518-55
Date
2011
Source
The Journal of biological chemistry   286(26): 23200-13 (Journal)
Registered Authors
Chen, Yu-Chia, Panula, Pertti
Keywords
brain, cell surface protein, cellular regulation, development, neuroscience, zebrafish, cell survival and proliferation, dopaminergic neurons, neural progenitors
MeSH Terms
  • Animals
  • Cell Proliferation/drug effects
  • Cell Survival/drug effects
  • Cell Survival/physiology
  • 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 Stem Cells/cytology
  • Neural Stem Cells/metabolism
  • Oligodeoxyribonucleotides, Antisense/pharmacology
  • Prosencephalon/cytology
  • Prosencephalon/embryology*
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish Proteins/biosynthesis*
  • Zebrafish Proteins/genetics
PubMed
21527633 Full text @ J. Biol. Chem.
Abstract
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 anti-sense oligonucleotides (MOs) or Hmgb1 cRNA. The HMGB1 knockdown morphants produced by injection of three different MOs 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 less cell groups expressing the transcription factor Pax6a in the forebrain and aberrant Wnt8 signalling. 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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping