title: High mobility group box-1 (HMGB1; amphoterin) is required for zebrafish brain development.
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 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.
authors.affiliation: Neuroscience Center, University of Helsinki, Helsinki FIN-00014, Finland.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhao
authors.forename: Juha
authors.initials: J
authors.lastname: Kuja-Panula
authors.forename: Ari
authors.initials: A
authors.lastname: Rouhiainen
authors.forename: Yu-chia
authors.initials: YC
authors.lastname: Chen
authors.forename: Pertti
authors.initials: P
authors.lastname: Panula
authors.forename: Heikki
authors.initials: H
authors.lastname: Rauvala
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D024243:HMGB1 Protein / Q000096:biosynthesis* / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D016548:Prosencephalon / Q000166:cytology / Q000196:embryology*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D024243:HMGB1 Protein; D009419:Nerve Tissue Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D029961:Zebrafish Proteins