title: Zebrafish dax1 is required for development of the interrenal organ, the adrenal cortex equivalent.
abstract: Mutations in the human nuclear receptor, DAX1, cause X-linked adrenal hypoplasia congenita (AHC). We report the isolation and characterization of a DAX1 homolog, dax1, in zebrafish. The dax1 cDNA encodes a protein of 264 amino acids, including the conserved carboxy-terminal ligand binding-like motif; but the amino-terminal region lacks the unusual repeats of the DNA binding-like domain in mammals. Genomic sequence analysis indicates that the dax1 gene structure is conserved also. Whole-mount in situ hybridization revealed the onset of dax1 expression in the developing hypothalamus at approximately 26 h post fertilization (hpf). Later, at about 28 hpf, a novel expression domain for dax1 appeared in the trunk. This bilateral dax1-expressing structure was located immediately above the yolk sac, between the otic vesicle and the pronephros. Interestingly, weak and transient expression of dax1 was observed in the interrenal glands (adrenal cortical equivalents) at approximately 31 hpf. This gene was also expressed in the liver after 3 dpf in the zebrafish larvae. Disruption of dax1 function by morpholino oligonucleotides (MO) down-regulated expression of steroidogenic genes, cyp11a and star, and led to severe phenotypes similar to ff1b (SF1) MO-injected embryos. Injection of dax1 MO did not affect ff1b expression, whereas ff1b MO abolished dax1 expression in the interrenal organ. Based on these results, we propose that dax1 is the mammalian DAX1 ortholog, functions downstream of ff1b in the regulatory cascades, and is required for normal development and function of the zebrafish interrenal organ.
authors.affiliation: Department of Pediatrics, David Geffen School of Medicine at UCLA, 10833 LeConte Avenue, Room 22-412 MDCC, Los Angeles, California 90095-1752, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.forename: Z
authors.initials: Z
authors.lastname: Yang
authors.forename: J K
authors.initials: JK
authors.lastname: Phelan
authors.forename: D A
authors.initials: DA
authors.lastname: Wheeler
authors.forename: S
authors.initials: S
authors.lastname: Lin
authors.forename: E R B
authors.initials: ER
authors.lastname: McCabe
mesh_terms: D000302:Adrenal Cortex / Q000196:embryology*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D004625:Embryo, Nonmammalian; D047108:Embryonic Development / Q000502:physiology; D007401:Interrenal Gland / Q000196:embryology*; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010802:Phylogeny; D018168:Receptors, Retinoic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000502:physiology; D014882:Water-Electrolyte Balance / Q000502:physiology; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000502:physiology
chemical_list: D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins; C539965:NR0B1 protein, human; D016376:Oligonucleotides, Antisense; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C478921:nr5a1a protein, zebrafish