title: Ectopic expression of Hoxa-1 in the zebrafish alters the fate of the mandibular arch neural crest and phenocopies a retinoic acid-induced phenotype.
abstract: Considerable evidence has demonstrated that retinoic acid influences the formation of the primary body axis in vertebrates and that this may occur through the regulation of Hox gene expression. In this study, we show that the phenotype induced by exogenous retinoic acid in the zebrafish can also be generated by the overexpression of Hoxa-1 following injection of synthetic RNA into the fertilised egg. The isolation, sequence and expression pattern of the zebrafish Hoxa-1 gene is described. We show that exogenously applied retinoic acid causes the ectopic accumulation of Hoxa-1 message during gastrulation in the hypoblast in the head region. Overexpression of Hoxa-1 following injection of RNA causes abnormal growth of the anterior hindbrain, duplication of Mauthner neurons in rhombomere (r) 2 and fate changes of r2 mesenchymal and neurogenic neural crest. These results are discussed in terms of the role of Hoxa-1 in controlling anterior hindbrain patterning and the relationship between expression of Hoxa-1 and retinoic acid.
authors.affiliation: Developmental Biology Research Centre, Randall Institute, King's College, London, UK.
authors.forename: D
authors.initials: D
authors.lastname: Alexandre
authors.forename: J D
authors.initials: JD
authors.lastname: Clarke
authors.forename: E
authors.initials: E
authors.lastname: Oxtoby
authors.forename: Y L
authors.initials: YL
authors.lastname: Yan
authors.forename: T
authors.initials: T
authors.lastname: Jowett
authors.forename: N
authors.initials: N
authors.lastname: Holder
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000378:metabolism; D008334:Mandible / Q000196:embryology*; D008969:Molecular Sequence Data; D009432:Neural Crest / Q000166:cytology*; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D012249:Rhombencephalon / Q000196:embryology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000502:physiology*; D014212:Tretinoin / Q000494:pharmacology; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; C088144:HoxA protein; D014212:Tretinoin