Cooperative roles of Bozozok/Dharma and Nodal-related proteins in the formation of the dorsal organizer in zebrafish

Shimizu, T., Yamanaka, Y., Ryu, S., Hashimoto, H., Yabe, T., Hirata, T., Bae, Y., Hibi, M., and Hirano, T.
Mechanisms of Development   91(1-2): 293-303 (Journal)
Registered Authors
Bae, Young Ki, Hashimoto, Hisashi, Hibi, Masahiko, Hirata, Tsutomu, Ryu, Seung-Lim, Shimizu, Takashi, Yabe, Taijirou, Yamanaka, Yojiro
zebrafish; dharma; bozozok; Nodal; squint; cyclops; Nieuwkoop center; Spemann organizer
MeSH Terms
  • Animals
  • Blastocyst/physiology
  • Body Patterning/physiology*
  • Calcium-Calmodulin-Dependent Protein Kinases/genetics
  • Calcium-Calmodulin-Dependent Protein Kinases/metabolism
  • Cytoskeletal Proteins/genetics
  • Cytoskeletal Proteins/metabolism
  • Gastrula/physiology
  • Gene Expression Regulation, Developmental
  • Glycogen Synthase Kinase 3
  • Glycoproteins*
  • Goosecoid Protein
  • Homeodomain Proteins/genetics
  • Homeodomain Proteins/metabolism*
  • Intercellular Signaling Peptides and Proteins*
  • Intracellular Signaling Peptides and Proteins
  • Nodal Signaling Ligands
  • Proteins/genetics
  • Repressor Proteins*
  • Time Factors
  • Trans-Activators*
  • Transcription Factors*
  • Transforming Growth Factor beta/genetics
  • Transforming Growth Factor beta/metabolism*
  • Zebrafish/embryology*
  • Zebrafish/physiology
  • Zebrafish Proteins*
  • beta Catenin
10704853 Full text @ Mech. Dev.
In vertebrates, specification of the dorso-ventral axis requires Wnt signaling, which leads to formation of the Nieuwkoop center and the Spemann organizer (dorsal organizer), through the nuclear accumulation of beta-catenin. Zebrafish bozozok/dharma (boz) and squint (sqt), which encode a homeodomain protein and a Nodal-related protein, respectively, are required for the formation of the dorsal organizer. The zygotic expression of boz and sqt in the dorsal blastoderm and dorsal yolk syncytial layer (YSL) was dependent on the maternally derived Wnt signal, and their expression at the late blastula and early gastrula stages was dependent on the zygotic expression of their own genes. The dorsal organizer genes, goosecoid (gsc) and chordin (din), were ectopically expressed in wild-type embryos injected with boz or sqt RNA. The expression of gsc strictly depended on both boz and sqt while the expression of din strongly depended on boz but only partially depended on sqt and cyclops (cyc, another nodal-related gene). Overexpression of boz in embryos defective in Nodal signaling elicited the ectopic expression of din but not gsc and resulted in dorsalization, implying that boz could induce part of the organizer, independent of the Nodal proteins. Furthermore, boz; sqt and boz;cyc double mutants displayed a severely ventralized phenotype with anterior truncation, compared with the single mutants, and boz;sqt;cyc triple mutant embryos exhibited an even more severe phenotype, lacking the anterior neuroectoderm and notochord, suggesting that Boz/Dharma and the Nodal-related proteins cooperatively regulate the formation of the dorsal organizer.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes