title: The homeobox gene bozozok promotes anterior neuroectoderm formation in zebrafish through negative regulation of BMP2/4 and Wnt pathways.
abstract: The neuroectoderm of the vertebrate gastrula was proposed by Nieuwkoop to be regionalized into forebrain, midbrain, hindbrain and spinal cord by a two-step process. In the activation step, the Spemann gastrula organizer induces neuroectoderm with anterior character, followed by posteriorization by a transforming signal. Recently, simultaneous inhibition of BMP and Wnt signaling was shown to induce head formation in frog embryos. However, how the inhibition of BMP and Wnt signaling pathways specify a properly patterned head, and how they are regulated in vivo, is not understood. Here we demonstrate that the loss of anterior neural fates observed in zebrafish bozozok (boz) mutants occurs during gastrulation due to a reduction and subsequent posteriorization of neuroectoderm. The neural induction defect was correlated with decreased chordino expression and consequent increases in bmp2b/4 expression, and was suppressed by overexpression of BMP antagonists. Whereas expression of anterior neural markers was restored by ectopic BMP inhibition in early boz gastrulae, it was not maintained during later gastrulation. The posteriorization of neuroectoderm in boz was correlated with ectopic dorsal wnt8 expression. Overexpression of a Wnt antagonist rescued formation of the organizer and anterior neural fates in boz mutants. We propose that boz specifies formation of anterior neuroectoderm by regulating BMP and Wnt pathways in a fashion consistent with Nieuwkoop's two-step neural patterning model. boz promotes neural induction by positively regulating organizer-derived chordino and limiting the antineuralizing activity of BMP2b/4 morphogens. In addition, by negative regulation of Wnt signaling, boz promotes organizer formation and limits posteriorization of neuroectoderm in the late gastrula.
authors.affiliation: Department of Molecular Biology, Vanderbilt University, Box 1820, Station B, Nashville, TN 37235, USA.
authors.forename: K
authors.initials: K
authors.lastname: Fekany-Lee
authors.forename: E
authors.initials: E
authors.lastname: Gonzalez
authors.forename: V
authors.initials: V
authors.lastname: Miller-Bertoglio
authors.forename: L
authors.initials: L
authors.lastname: Solnica-Krezel
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000196:embryology*; D004475:Ectoderm / Q000502:physiology*; D005775:Gastrula / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D016296:Mutagenesis; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000502:physiology; D029961:Zebrafish Proteins
chemical_list: D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D018398:Homeodomain Proteins; D011518:Proto-Oncogene Proteins; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C525813:bmp4 protein, zebrafish; C113874:dharma protein, zebrafish; C094522:wnt8b protein, zebrafish