Xenopus Zic-related-1 and Sox-2, two factors induced by chordin, have distinct activities in the initiation of neural induction.
In a differential screen for downstream genes of the neural inducers, we identified two extremely early neural genes induced by Chordin and suppressed by BMP-4: Zic-related-1 (Zic-r1), a zinc finger factor related to the Drosophila pair-rule gene odd-paired, and Sox-2, a Sry-related HMG factor. Expression of the two genes is first detected widely in the prospective neuroectoderm at the beginning of gastrulation, following the onset of Chordin expression and preceding that of Neurogenin (Xngnr-1). Zic-r1 mRNA injection activates the proneural gene Xngnr-1, and initiates neural and neuronal differentiation in isolated animal caps and in vivo. In contrast, Sox-2 alone is not sufficient to cause neural differentiation, but can work synergistically with FGF signaling to initiate neural induction. Thus, Zic-r1 acts in the pathway bridging the neural inducer with the downstream proneural genes, while Sox-2 makes the ectoderm responsive to extracellular signals, demonstrating that the early phase of neural induction involves simultaneous activation of multiple functions.
Mizuseki
K
K
Department of Biological Sciences, Kyoto University Faculty of Medicine, Yoshida, Sakyo, Kyoto 606, Japan.
Kishi
M
M
Matsui
M
M
Nakanishi
S
S
Sasai
Y
Y
D000818:Animals; D001483:Base Sequence; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006023:Glycoproteins; D006133:Growth Substances / Q000494:pharmacology*; D024002:HMGB Proteins; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D008845:Microinjections; D009420:Nervous System / Q000254:growth & development*; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000008:administration & dosage / Q000235:genetics; D055748:SOXB1 Transcription Factors; D015398:Signal Transduction; D014157:Transcription Factors; D014981:Xenopus / Q000235:genetics* / Q000254:growth & development*; D029867:Xenopus Proteins; D016335:Zinc Fingers / Q000235:genetics / Q000502:physiology*
D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D006023:Glycoproteins; D006133:Growth Substances; D024002:HMGB Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors; D029867:Xenopus Proteins; C525812:bmp4 protein, Xenopus; C527781:sox2 protein, Xenopus; D005346:Fibroblast Growth Factors; C054234:chordin