XB-ART-45526Dev Biol August 15, 2012; 368 (2): 231-41.
Transcriptional integration of Wnt and Nodal pathways in establishment of the Spemann organizer.
Signaling inputs from multiple pathways are essential for the establishment of distinct cell and tissue types in the embryo. Therefore, multiple signals must be integrated to activate gene expression and confer cell fate, but little is known about how this occurs at the level of target gene promoters. During early embryogenesis, Wnt and Nodal signals are required for formation of the Spemann organizer, which is essential for germ layer patterning and axis formation. Signaling by both Wnt and Nodal pathways is required for the expression of multiple organizer genes, suggesting that integration of these signals is required for organizer formation. Here, we demonstrate transcriptional cooperation between the Wnt and Nodal pathways in the activation of the organizer genes Goosecoid (Gsc), Cerberus (Cer), and Chordin (Chd). Combined Wnt and Nodal signaling synergistically activates transcription of these organizer genes. Effectors of both pathways occupy the Gsc, Cer and Chd promoters and effector occupancy is enhanced with active Wnt and Nodal signaling. This suggests that, at organizer gene promoters, a stable transcriptional complex containing effectors of both pathways forms in response to combined Wnt and Nodal signaling. Consistent with this idea, the histone acetyltransferase p300 is recruited to organizer promoters in a Wnt and Nodal effector-dependent manner. Taken together, these results offer a mechanism for spatial and temporal restriction of organizer gene transcription by the integration of two major signaling pathways, thus establishing the Spemann organizer domain.
PubMed ID: 22627292
PMC ID: PMC3572767
Article link: Dev Biol
Species referenced: Xenopus laevis
Genes referenced: cer1 chrd.1 crebbp ep300 foxh1.2 gsc mst1 myc myl2 nodal nodal1 sia1
Article Images: [+] show captions
|Fig. 3. Wnt pathway effectors occupy organizer gene promoters. Genomic regions recovered by chromatin immunoprecipitation (ChIP) from embryos injected with 50 pg myc-Sia, 50 pg myc-Twn or 50 pg of a DNA-binding inactive Sia (myc-SiaQ191E) were evaluated by quantitative PCR (QPCR) for the (A) Gsc, (B) Cer, or (C) Chd promoters. Immunoprecipitation using anti-myc antibody was performed on uninjected embryos (Control). The mean fold enrichment (normalized to uninjected samples) and standard error for five independent experiments is presented. The white bars represent QPCR for genomic Xmlc2 as a control.|
|Fig. 5. Siamois/Twin occupancy at organizer promoters is enhanced by Nodal signaling. Genomic regions recovered by ChIP for 10 pg myc-Sia, 10 pg myc-Sia and 50 pg Xnr1, 10 pg myc-Twn, or 10 pg myc-Twn and 50 pg Xnr1 were evaluated by QPCR for the (A) Gsc, (B) Cer or (C) Chd promoters. The white bars represent QPCR for genomic EF1α as a control. The mean fold enrichment (normalized to uninjected samples) and standard error for eight independent experiments is presented.|
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