title: The forkhead transcription factor FoxB1 regulates the dorsal-ventral and anterior-posterior patterning of the ectoderm during early Xenopus embryogenesis.
abstract: The formation of the dorsal-ventral (DV) and anterior-posterior (AP) axes, fundamental to the body plan of animals, is regulated by several groups of polypeptide growth factors including the TGF-β, FGF, and Wnt families. In order to ensure the establishment of the body plan, the processes of DV and AP axis formation must be linked and coordinately regulated. However, the molecular mechanisms responsible for these interactions remain unclear. Here, we demonstrate that the forkhead box transcription factor FoxB1, which is upregulated by the neuralizing factor Oct-25, plays an important role in the formation of the DV and AP axes. Overexpression of FoxB1 promoted neural induction and inhibited BMP-dependent epidermal differentiation in ectodermal explants, thereby regulating the DV patterning of the ectoderm. In addition, FoxB1 was also found to promote the formation of posterior neural tissue in both ectodermal explants and whole embryos, suggesting its involvement in embryonic AP patterning. Using knockdown analysis, we found that FoxB1 is required for the formation of posterior neural tissues, acting in concert with the Wnt and FGF pathways. Consistent with this, FoxB1 suppressed the formation of anterior structures via a process requiring the function of XWnt-8 and eFGF. Interestingly, while downregulation of FoxB1 had little effect on neural induction, we found that it functionally interacted with its upstream factor Oct-25 and plays a supportive role in the induction and/or maintenance of neural tissue. Our results suggest that FoxB1 is part of a mechanism that fine-tunes, and leads to the coordinated formation of, the DV and AP axes during early development.
authors.affiliation: Institute for Amphibian Biology, Hiroshima University Graduate School of Science, Kagamiyama 1-3-1, Higashi-Hiroshima, Japan.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Takebayashi-Suzuki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kitayama
authors.forename: Chie
authors.initials: C
authors.lastname: Terasaka-Iioka
authors.forename: Naoto
authors.initials: N
authors.lastname: Ueno
authors.forename: Atsushi
authors.initials: A
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D001483:Base Sequence; D019521:Body Patterning / Q000235:genetics / Q000502:physiology*; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D004475:Ectoderm / Q000196:embryology / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000502:physiology; D051858:Forkhead Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D060172:Morpholinos / Q000235:genetics; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology; D016376:Oligonucleotides, Antisense / Q000235:genetics; D050809:POU Domain Factors / Q000502:physiology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D015854:Up-Regulation; D051153:Wnt Proteins / Q000502:physiology; D060449:Wnt Signaling Pathway; D029867:Xenopus Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000502:physiology*
chemical_list: D019485:Bone Morphogenetic Proteins; C528532:FGF4 protein, Xenopus; D051858:Forkhead Transcription Factors; D060172:Morpholinos; D016376:Oligonucleotides, Antisense; D050809:POU Domain Factors; D011994:Recombinant Proteins; D051153:Wnt Proteins; D029867:Xenopus Proteins; C527329:pou5f3.2 protein, Xenopus; C495248:wnt8a protein, Xenopus; D005346:Fibroblast Growth Factors