Inactivation of the zebrafish homologue of Chx10 by antisense oligonucleotides causes eye malformations similar to the ocular retardation phenotype.
We report the cloning of a zebrafish paired-type homeobox gene, Alx, closely related to the murine Chx10 and the gold fish Vsx-I homeodomain proteins. Alx is first expressed at about 12 h post-fertilization (hpf) when optic vesicles appear. Its expression is restricted to the early retinal neuroepithelium, whereas no signal can be detected in the optic placode. Later, Alx expression follows the differentiation of the neural retina. Inhibition experiments with antisense oligonucleotides resulted in specific eye malformations which are reminiscent of the phenotype of ocular retardation (or) mice, caused by a spontaneous Chx10 mutation. The expression of other developmentally relevant genes such as pax(zf-a), pax(zf-b) and krx-20 was not affected in the antisense treated embryos.
Barabino
S M
SM
DIBIT, H S Raffaele Scientific Institute, Milan, Italy. Barabino@ubaclu.unibas.ch
Spada
F
F
Cotelli
F
F
Boncinelli
E
E
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D004305:Dose-Response Relationship, Drug; D005124:Eye Abnormalities / Q000235:genetics / Q000503:physiopathology*; D005136:Eye Proteins / Q000096:biosynthesis / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D014018:Tissue Distribution; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics*; D029961:Zebrafish Proteins
D005136:Eye Proteins; D018398:Homeodomain Proteins; D016376:Oligonucleotides, Antisense; D014157:Transcription Factors; D029961:Zebrafish Proteins; C108000:vsx2 protein, zebrafish