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Mech Dev
2007 Jan 01;12411-12:840-55. doi: 10.1016/j.mod.2007.09.005.
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The Xenopus POU class V transcription factor XOct-25 inhibits ectodermal competence to respond to bone morphogenetic protein-mediated embryonic induction.
Takebayashi-Suzuki K
,
Arita N
,
Murasaki E
,
Suzuki A
.
???displayArticle.abstract??? Bone morphogenetic proteins (BMPs) have been shown to play a key role in controlling ectodermal cell fates by inducing epidermis at the expense of neural tissue during gastrulation. Here, we present evidence that the Xenopus POU class V transcription factor XOct-25 regulates ectodermal cell fate decisions by inhibiting the competence of ectodermal cells to respond to BMP during Xenopus embryogenesis. When overexpressed in the ectoderm after the blastula stage, XOct-25 suppressed early BMP responses of ectodermal cells downstream of BMP receptor activation and promoted neural induction while suppressing epidermal differentiation. In contrast, inhibition of XOct-25 function in the prospective neuroectoderm resulted in expansion of epidermal ectoderm at the expense of neuroectoderm. The reduction of neural tissue by inhibition of XOct-25 function could be rescued by decreasing endogenous BMP signaling, suggesting that XOct-25 plays a role in the formation of neural tissue at least in part by inhibiting BMP-mediated epidermal induction (neural inhibition). This hypothesis is supported by the observation that ectodermal cells from XOct-25 morphants were more sensitive to BMP signaling than cells from controls in inducing both immediate early BMP target genes and epidermis at the expense of neural tissue, while cells overexpressing XOct-25 are less competent to respond to BMP-mediated induction. These results document an essential role for XOct-25 in commitment to neural or epidermal cell fates in the ectoderm and highlight the importance of a regulatory mechanism that limits competence to respond to BMP-mediated embryonic induction.
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17950579
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Fig. 2. XOct-25 promotes commitment to neural fate at the expense of epidermal fate. The phenotypes of neurula stage embryos coinjected with GR-XOct-25 mRNA (500 pg) together with β-galactosidase (β-gal) mRNA into either one of the dorsal animal blastomeres at the 8-cell stage (A, B, E, F and IâP) or one of the ventral animal blastomeres at the 16-cell stage (G and H). In C and D, mRNA was injected unilaterally into both dorsal and ventral animal blastomeres of 8-cell stage embryos in order to determine the effect on the epidermal region. Except for controls, injected embryos were treated with DEX from the blastula stage to activate GR-XOct-25 (Oct). The overexpression of GR-XOct-25 expanded the neural plate marker Sox2 at the expense of the epidermal markers epidermal keratin and Dlx3 (compare B with D and F). In the neuroectoderm, GR-XOct-25 moderately suppressed the expression of the neuronal markers N-tubulin and Xngnr-1 (J and L). There was no effect on the expression of the mesodermal markers chordin and MyoD by XOct-25 overexpression (N and P). The expression of marker genes is shown in purple. β-gal was stained in red and the injected side of the embryo is indicated by brackets. AâF and M: frontal view; N: dorso-frontal view; G and H: ventral view; IâL, O and P: dorsal view.
Fig. 4. Perturbation of XOct-25 function in the ectoderm during embryogenesis. The phenotypes of neurula stage embryos coinjected with either Oct MO or 6-mismatch control MO together with β-gal mRNA into one of the dorsal animal blastomeres at the 8-cell stage. The amounts of injected antisense oligonucleotides per embryo were 5.6 ng (AâC) and 4.3 ng (GâP) for moderate amounts, and 8.6 ng (DâF) as a large amount. The reduction of Sox2 expression by Oct MO injection was rescued by coinjection of δBMPR mRNA (500 pg, C) or GR-mutXOct-25 mRNA (250 pg, F). Note that cells receiving Oct MO expressed the epidermal markers epidermal keratin and Dlx3 at the expense of the neural marker Sox2 (B, H, I, K and L). There was no effect on the expression of the mesodermal markers chordin and MyoD by XOct-25 knockdown (N and P). The expression of marker genes is shown in purple. β-gal was stained in red and the injected side of the embryo is indicated by brackets. I and L are magnifications of H and K, respectively. The edges of ectopic epidermal marker expression are indicated by dashed lines (I and L). AâF, O and P: dorsal view; GâL and N: frontal view; M: dorso-frontal view.