title: The response of HMGA1 to changes in oxygen availability is evolutionarily conserved.
abstract: Zebrafish embryos have evolved to cope with hypoxia during development. This includes the ability to completely suspend embryo development for extended periods until normoxia is restored. However, only a limited number of studies have examined the gene regulatory responses of zebrafish embryos to hypoxia. The High Mobility Group A1 protein encoded by the mammalian gene HMGA1 is widely expressed during embryo development but not in adults. Its expression can be induced in adult neurons by hypoxia/oxidative stress and it is commonly reactivated in many types of cancer. We report the identification by phylogenetic and conserved synteny analyses of an HMGA1 orthologue in zebrafish, hmga1 (hmg-i/y) and analysis of sodium azide as a chemical agent for inducing hypoxia-like responses in zebrafish embryos including temporary suspension of development ("suspended animation"). Evidence was only found for the existence of the "a" isoform of HMGA1 in fish. The "b" and "c" isoforms were not detected. We show that zebrafish hmga1 is expressed in a manner similar to in mammals including its induction by hypoxia during hatching stage and in adult zebrafish brain. However, earlier during development, hypoxia causes a decrease in hmga1 transcript levels. By analysis of conservation of the HMGA1a isoform binding site in zebrafish psen2 gene transcripts, we predict that a zebrafish equivalent of the PS2V isoform of human PSEN2 is not formed and we support this by RT-PCR analyses. Thus, analysis of hmga1 function in zebrafish embryogenesis may be valuable for understanding its wider role in vertebrate development, cancer and cellular responses to hypoxia but not for analysis of the action of HMGA1 in PS2V formation.
authors.affiliation: Discipline of Genetics, School of Molecular and Biomedical Sciences, The University of Adelaide, Australia. seyyed.moussavinik@adelaide.edu.au
authors.forename: Seyyed Hani
authors.initials: SH
authors.lastname: Moussavi Nik
authors.forename: Morgan
authors.initials: M
authors.lastname: Newman
authors.forename: Michael
authors.initials: M
authors.lastname: Lardelli
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism*; D025741:HMGA1a Protein / Q000235:genetics / Q000378:metabolism*; D000860:Hypoxia; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D010100:Oxygen / Q000378:metabolism*; D010802:Phylogeny; D053766:Presenilin-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D015027:Zebrafish / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D053766:Presenilin-2; C543888:Psen2 protein, zebrafish; D012333:RNA, Messenger; D029961:Zebrafish Proteins; D025741:HMGA1a Protein; D010100:Oxygen