High impact information on dharma

• In this report we have isolated a novel zebrafish homeobox gene, dharma, capable of inducing the organizer ectopically [1].
• The expression of dharma was first detected in several blastomeres at one side of the margin soon after the mid-blastula transition and continued in the dorsal side of the yolk syncytial layer (YSL) under the embryonic shield, the zebrafish organizer, until the onset of gastrulation [1].
• A novel homeobox gene, dharma, can induce the organizer in a non-cell-autonomous manner [1].
• The area affected by the DN-p38 expression did not correlate with the initial cleavage plane, but coincided with the side where dharma/bozozok, a dorsal-specific zygotic gene, was expressed (Yamanaka et al. 1998) [2].
• Antagonistic role of vega1 and bozozok/dharma homeobox genes in organizer formation [3].

Biological context of dharma

• Injection of RNAs for activated beta-catenin, dominant-negative forms of Axin1 and GSK3beta, and wild-type Dvl3, into the tkk embryos suppressed the ventralized phenotypes and/or dorsalized the embryos, and restored or induced an ectopic and expanded expression of bozozok/dharma and goosecoid [4].
• The nieuwkoid/dharma homeobox gene is essential for bmp2b repression in the zebrafish pregastrula [5].
• Furthermore, ectopic expression of nieuwkoid/dharma RNA is sufficient to lead to the down regulation of zbmp2b expression in the pregastrula [5].
• A single base-pair substitution in the nieuwkoid/dharma gene results in a premature stop codon in boz(m168) mutants, leading to the generation of a truncated protein product which lacks the homeodomain and fails to induce a functional organizer in misexpression assays [5].
• This promoter region recapitulated the Wnt-dependent and dorsal dharma expression pattern when it was fused to luciferase or GFP [6].

Anatomical context of dharma

• Based on these results, we propose that gastrula organizer specification requires the Nieuwkoop center-like activity mediated by the nieuwkoid/dharma/bozozok homeobox gene and that this activity reveals the role of a much earlier than previously suspected inhibition of ventral determinants prior to dorsal shield formation [5].
• Furthermore, boz homozygotes feature a loss of neural fates anterior to the midbrain/hindbrain boundary [5].
• The zebrafish bozozok (boz) gene encoding a homeodomain protein (also named Dharma/Nieuwkoid) is required during blastula stages for the formation of a complete Spemann-Mangold gastrula organizer and subsequent development of axial mesoderm and anterior neural structures [7].

Regulatory relationships of dharma

• The gastrula organizer forms in the dorsal region of the zebrafish embryo, where the bozozok/dharma homeobox gene downregulates expression of the vega1 transcriptional repressor [8].

Other interactions of dharma

• Cooperative roles of Bozozok/Dharma and Nodal-related proteins in the formation of the dorsal organizer in zebrafish [9].
• The vertebrate Vox/Vent family of transcription factors plays a crucial role in the establishment of the dorsoventral (DV) axis, by repressing organizer genes such as bozozok/dharma, goosecoid, and chordino [10].
• Dharma/Bozozok (Dha/Boz) is a homeodomain protein containing an Engrailed homology (Eh) 1 repressor motif [11].

References