The role of the homeodomain protein Bozozok in Zebrafish axis formation

The zebrafish bororok (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. Expression of borin the dor sal yolk syncytial layer (YSL) and overlying marginal blastomeres is activa ted by beta -catenin. Bozozok itself acts as a transcriptional repressor, a nd promotes organizer formation by directly inhibiting expression of the bm p2b (swirl) gene and by negatively regulating Wnt signaling by an unknown m echanism. boz cooperates with the Nodal-related secreted factors, Cyclops a nd Squint, in organizer formation. The incomplete organizer in boz mutants is deficient in expression of a number of factors such as Chordin that anta gonize Bone morphogenetic proteins (Bmps), and Dickitopf 1, a Wnt antagonis t. Conversely, the dorsal blastoderm of boz mutants exhibits ectopic expres sion of genes normally excluded from the dorsal midline such as wnt8 or tbx 6. boz specifies the formation of anterior neuroectoderm by regulating Bmp and Wnt pathways in a fashion consistent with Nieuwkoop's two-step neural p atterning model. boz promotes neural induction by limiting the anti-neurali zing activity of Bmp morphogens. In addition, by negative regulation of Wnt signaling, boz limits posteriorization of neuroectoderm. bororok chordino double mutants exhibit a synergistic loss of head and trunk. This synthetic phenotype is due to dramatically increased Bmp signaling and consequent ma ssive accumulation of cells in the tailbud at the expense of dorso-anterior structures. Therefore, boz and din act in overlapping pathways that provid e the main mechanism to limit Bmp signaling in the zebrafish gastrula and a llow for head and trunk development. Notably, appears to function by repres sing transcription of target genes such as swr(bmp26) gene, and as such is the earliest acting repressor that the nascent dorsal axis is using to anta gonize ventral influences.