title: Transcriptional integration of Wnt and Nodal pathways in establishment of the Spemann organizer.
abstract: 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.
authors.affiliation: Department of Cell and Developmental Biology, University of Pennsylvania, School of Medicine, Room 1110 Biomedical Research Building 2/3, 421 Curie Boulevard, Philadelphia, PA 19104-6058, USA.
authors.forename: Christine D
authors.initials: CD
authors.lastname: Reid
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Michael D
authors.initials: MD
authors.lastname: Sheets
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Kessler
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D051956:Goosecoid Protein / Q000235:genetics; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D055457:Nodal Protein / Q000235:genetics / Q000378:metabolism*; D020897:Organizers, Embryonic / Q000196:embryology / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D013997:Time Factors; D015533:Transcriptional Activation; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology / Q000378:metabolism; D050880:p300-CBP Transcription Factors / Q000235:genetics / Q000378:metabolism; D000099224:p300-CBP-Associated Factor
chemical_list: D051956:Goosecoid Protein; D036341:Intercellular Signaling Peptides and Proteins; D055457:Nodal Protein; D051153:Wnt Proteins; D029867:Xenopus Proteins; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C100866:cer1 protein, Xenopus