The zebrafish bozozok locus encodes Dharma, a homeodomain protein essential for induction of gastrula organizer and dorsoanterior embryonic structures

Fekany, K., Yamanaka, Y., Leung, T., Sirotkin, H.I., Topczewski, J., Gates, M.A., Hibi, M., Renucci, A., Stemple, D., Radbill, A., Schier, A.F., Driever, W., Hirano, T., Talbot, W.S., and Solnica-Krezel, L.
Development (Cambridge, England)   126: 1427-1438 (Journal)
Registered Authors
Driever, Wolfgang, Fekany-Lee, Kimberly, Gates, Michael A., Hibi, Masahiko, Leung, Tin Chung, Renucci, Armand, Schier, Alexander, Sirotkin, Howard, Solnica-Krezel, Lilianna, Stemple, Derek L., Talbot, William S., Topczewski, Jacek, Yamanaka, Yojiro
Spemann organizer; Nieuwkoop center; notochord; prechordal mesendoderm; dorsal forerunner cells; A-P patterning; bozozok; axis
MeSH Terms
  • Animals
  • Brain/embryology
  • Cytoskeletal Proteins/genetics
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins/genetics*
  • Immunohistochemistry
  • In Situ Hybridization
  • Mutation
  • Notochord/embryology
  • RNA, Messenger/metabolism
  • Signal Transduction/genetics
  • Trans-Activators*
  • Transforming Growth Factor beta/genetics
  • Zebrafish/embryology*
  • Zebrafish Proteins*
  • beta Catenin
10068636 Full text @ Development
The dorsal gastrula organizer plays a fundamental role in establishment of the vertebrate axis. We demonstrate that the zebrafish bozozok (boz) locus is required at the blastula stages for formation of the embryonic shield, the equivalent of the gastrula organizer and expression of multiple organizer-specific genes. Furthermore, boz is essential for specification of dorsoanterior embryonic structures, including notochord, prechordal mesendoderm, floor plate and forebrain. We report that boz mutations disrupt the homeobox gene dharma. Overexpression of boz in the extraembryonic yolk syncytial layer of boz mutant embryos is sufficient for normal development of the overlying blastoderm, revealing an involvement of extraembryonic structures in anterior patterning in fish similarly to murine embryos. Epistatic analyses indicate that boz acts downstream of ß-catenin and upstream to TGF-ß signaling or in a parallel pathway. These studies provide genetic evidence for an essential function of a homeodomain protein in ß-catenin-mediated induction of the dorsal gastrula organizer and place boz at the top of a hierarchy of zygotic genes specifying the dorsal midline of a vertebrate embryo.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes