Conversion of ectoderm into a neural fate by ATH-3, a vertebrate basic helix-loop-helix gene homologous to Drosophila proneural gene atonal.
We have isolated a novel basic helix-loop-helix (bHLH) gene homologous to the Drosophila proneural gene atonal, termed ATH-3, from Xenopus and mouse. ATH-3 is expressed in the developing nervous system, with high levels of expression in the brain, retina and cranial ganglions. Injection of ATH-3 RNA into Xenopus embryos dramatically expands the neural tube and induces ectopic neural tissues in the epidermis but inhibits non-neural development. This ATH-3-induced neural hyperplasia does not require cell division, indicating that surrounding cells which are normally non-neural types adopt a neural fate. In a Xenopus animal cap assay, ATH-3 is able to convert ectodermal cells into neurons expressing anterior markers without inducing mesoderm. Interestingly, a single amino acid change from Ser to Asp in the basic region, which mimics phosphorylation of Ser, severely impairs the anterior marker-inducing ability without affecting general neurogenic activities. These results provide evidence that ATH-3 can directly convert non-neural or undetermined cells into a neural fate, and suggest that the Ser residue in the basic region may be critical for the regulation of ATH-3 activity by phosphorylation.
Takebayashi
K
K
Department of Biological Sciences, Kyoto University Faculty of Medicine, Yoshida, Sakyo-ku, Japan.
Takahashi
S
S
Yokota
C
C
Tsuda
H
H
Nakanishi
S
S
Asashima
M
M
Kageyama
R
R
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D015152:Blotting, Northern; D002490:Central Nervous System / Q000196:embryology*; D004268:DNA-Binding Proteins / Q000502:physiology*; D004330:Drosophila; D029721:Drosophila Proteins; D004475:Ectoderm / Q000166:cytology*; D018507:Gene Expression Regulation, Developmental; D018257:Helix-Loop-Helix Motifs; D017403:In Situ Hybridization; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D012313:RNA / Q000378:metabolism; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D014981:Xenopus; D029867:Xenopus Proteins
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; D012313:RNA; D029867:Xenopus Proteins; C500943:Atoh1 protein, mouse; C491279:NEUROD4 protein, Xenopus; C104516:Neurod4 protein, mouse; C082142:ato protein, Drosophila