title: Chordin and dickkopf-1b are essential for the formation of head structures through activation of the FGF signaling pathway in zebrafish.
abstract: The ability of the Spemann organizer to induce dorsal axis formation is dependent on downstream factors of the maternal Wnt/β-catenin signaling pathway. The fibroblast growth factor (FGF) signaling pathway has been identified as one of the downstream components of the maternal Wnt/β-catenin signaling pathway. The ability of the FGF signaling pathway to induce the formation of a dorsal axis with a complete head structure requires chordin (chd) expression; however, the molecular mechanisms involved in this developmental process, due to activation of FGF signaling, remain unclear. In this study, we showed that activation of the FGF signaling pathway induced the formation of complete head structures through the expression of chd and dickkopf-1b (dkk1b). Using the organizer-deficient maternal mutant, ichabod, we identified dkk1b as a novel downstream factor in the FGF signaling pathway. We also demonstrate that dkk1b expression is necessary, after activation of the FGF signaling pathway, to induce neuroectoderm patterning along the anteroposterior (AP) axis and for formation of complete head structures. Co-injection of chd and dkk1b mRNA resulted in the formation of a dorsal axis with a complete head structure in ichabod embryos, confirming the role of these factors in this developmental process. Unexpectedly, we found that chd induced dkk1b expression in ichabod embryos at the shield stage. However, chd failed to maintain dkk1b expression levels in cells of the shield and, subsequently, in the cells of the prechordal plate after mid-gastrula stage. In contrast, activation of the FGF signaling pathway maintained the dkk1b expression from the beginning of gastrulation to early somitogenesis. In conclusion, activation of the FGF signaling pathway induces the formation of a dorsal axis with a complete head structure through the expression of chd and subsequent maintenance of dkk1b expression levels.
authors.affiliation: Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Department of Intelligence Science and Technology, Graduate School of Informatics, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hosokawa
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Weinberg
authors.affiliation: Department of Intelligence Science and Technology, Graduate School of Informatics, Kyoto University, Kyoto 606-8501, Japan. Electronic address: shingo@i.kyoto-u.ac.jp.
authors.forename: Shingo
authors.initials: S
authors.lastname: Maegawa
mesh_terms: D000818:Animals; D019521:Body Patterning; D004625:Embryo, Nonmammalian / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D054262:Gastrulation; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000378:metabolism*; D006257:Head / Q000196:embryology*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D054258:Neural Plate / Q000196:embryology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D019170:Somites / Q000196:embryology / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D029961:Zebrafish Proteins; C501128:dkk1b protein, zebrafish; D005346:Fibroblast Growth Factors; C054234:chordin
keywords: FGF signaling; Head induction; The Spemann organizer; chordin; dickkopf-1b