Zhu K , Spaink HP , Durston AJ .

             BMP signaling pathway
             head development

	Figure 1. Timed Noggin-injection in wild-type embryos resulted in progressive arrest of head patterning: 200 nL of 1 ng/µL Noggin was injected into the blastocoel of the embryo at different stages. Anterior is to the left and dorsal is up. Black arrows point to the position of the cement gland. These experiments were repeated at least three times and more than 80 embryos were used for each time point.
	Figure 2. Timed anti-BMP treatments in ventralized embryos led to sequential fixation of anterior genes. The expression of xcg-1, six3, otx2, gbx2, and hoxd1 in bmp4-injected embryos that were subjected to Smad6 treatment at different stages. These experiments were repeated at least three times and >40 embryos were used for each condition. Black arrows indicate the anterior borders of the expression domains.
	Figure 3. The expression of six3, otx2, gbx2 and hoxd1 at different stages in wild-type and smad6-injected embryos. Embryos are vegetal views with dorsal to the top. These experiments were repeated at least three times and >40 embryos were used for each condition.
	Figure 4. Hypothesis for head patterning by BMP signaling. A currently unknown, BMP-dependent timer is running during head patterning. The timer can be fixed by anti-BMP signals and regulates the expression of anterior genes: xcg-1, six3, otx2, gbx2, and hoxd1, resulting in the head being progressively patterned.

Alexandre, Ectopic expression of Hoxa-1 in the zebrafish alters the fate of the mandibular arch neural crest and phenocopies a retinoic acid-induced phenotype. 1996, Pubmed

Alexandre, Ectopic expression of Hoxa-1 in the zebrafish alters the fate of the mandibular arch neural crest and phenocopies a retinoic acid-induced phenotype. 1996, Pubmed
Blitz, Anterior neurectoderm is progressively induced during gastrulation: the role of the Xenopus homeobox gene orthodenticle. 1995, Pubmed , Xenbase
Clement, Bone morphogenetic protein 2 in the early development of Xenopus laevis. 1995, Pubmed , Xenbase
Cooke, Gastrulation and larval pattern in Xenopus after blastocoelic injection of a Xenopus-derived inducing factor: experiments testing models for the normal organization of mesoderm. 1989, Pubmed , Xenbase
Dale, Bone morphogenetic protein 4: a ventralizing factor in early Xenopus development. 1992, Pubmed , Xenbase
Dias, Somites without a clock. 2014, Pubmed
Dickinson, Positioning the extreme anterior in Xenopus: cement gland, primary mouth and anterior pituitary. 2007, Pubmed , Xenbase
Duboule, The structural and functional organization of the murine HOX gene family resembles that of Drosophila homeotic genes. 1989, Pubmed
Durston, A time space translation hypothesis for vertebrate axial patterning. 2015, Pubmed , Xenbase
EYAL-GILADI, Dynamic aspects of neural induction in amphibia. 1954, Pubmed
Fang, Ectopic expression of Xenopus noggin RNA induces complete secondary body axes in embryos of the direct developing frog Eleutherodactylus coqui. 2000, Pubmed , Xenbase
Gammill, Coincidence of otx2 and BMP4 signaling correlates with Xenopus cement gland formation. 2000, Pubmed , Xenbase
Gamse, Vertebrate anteroposterior patterning: the Xenopus neurectoderm as a paradigm. 2000, Pubmed , Xenbase
Gamse, Early anteroposterior division of the presumptive neurectoderm in Xenopus. 2001, Pubmed , Xenbase
Goto, Selective inhibitory effects of Smad6 on bone morphogenetic protein type I receptors. 2007, Pubmed
Graham, The murine and Drosophila homeobox gene complexes have common features of organization and expression. 1989, Pubmed
Hashiguchi, Anteroposterior and dorsoventral patterning are coordinated by an identical patterning clock. 2013, Pubmed , Xenbase
Hata, Smad6 inhibits BMP/Smad1 signaling by specifically competing with the Smad4 tumor suppressor. 1998, Pubmed , Xenbase
Imamura, Smad6 inhibits signalling by the TGF-beta superfamily. 1997, Pubmed
Jacox, The extreme anterior domain is an essential craniofacial organizer acting through Kinin-Kallikrein signaling. 2014, Pubmed , Xenbase
Jones, DVR-4 (bone morphogenetic protein-4) as a posterior-ventralizing factor in Xenopus mesoderm induction. 1992, Pubmed , Xenbase
Kao, The entire mesodermal mantle behaves as Spemann's organizer in dorsoanterior enhanced Xenopus laevis embryos. 1988, Pubmed , Xenbase
Kenyon, A novel fork head gene mediates early steps during Xenopus lens formation. 1999, Pubmed , Xenbase
Kessel, Homeotic transformations of murine vertebrae and concomitant alteration of Hox codes induced by retinoic acid. 1991, Pubmed
Khokha, Depletion of three BMP antagonists from Spemann's organizer leads to a catastrophic loss of dorsal structures. 2005, Pubmed , Xenbase
Kobayashi, Overexpression of the forebrain-specific homeobox gene six3 induces rostral forebrain enlargement in zebrafish. 1998, Pubmed
Lewis, A gene complex controlling segmentation in Drosophila. 1978, Pubmed
Li, Expression of two zebrafish orthodenticle-related genes in the embryonic brain. 1994, Pubmed
Marom, Temporal analysis of the early BMP functions identifies distinct anti-organizer and mesoderm patterning phases. 2005, Pubmed , Xenbase
Mori, Different spatio-temporal expressions of three otx homeoprotein transcripts during zebrafish embryogenesis. 1994, Pubmed
Nishimatsu, Genes for bone morphogenetic proteins are differentially transcribed in early amphibian embryos. 1992, Pubmed , Xenbase
Oliver, Six3, a murine homologue of the sine oculis gene, demarcates the most anterior border of the developing neural plate and is expressed during eye development. 1995, Pubmed
Rhinn, Cloning, expression and relationship of zebrafish gbx1 and gbx2 genes to Fgf signaling. 2003, Pubmed
Sasai, Xenopus chordin: a novel dorsalizing factor activated by organizer-specific homeobox genes. 1994, Pubmed , Xenbase
Scharf, Axis determination in eggs of Xenopus laevis: a critical period before first cleavage, identified by the common effects of cold, pressure and ultraviolet irradiation. 1983, Pubmed , Xenbase
Schmidt, Localized BMP-4 mediates dorsal/ventral patterning in the early Xenopus embryo. 1995, Pubmed , Xenbase
Sive, Progressive determination during formation of the anteroposterior axis in Xenopus laevis. 1989, Pubmed , Xenbase
Sive, Retinoic acid perturbs the expression of Xhox.lab genes and alters mesodermal determination in Xenopus laevis. 1991, Pubmed , Xenbase
Smith, Expression cloning of noggin, a new dorsalizing factor localized to the Spemann organizer in Xenopus embryos. 1992, Pubmed , Xenbase
Smith, Secreted noggin protein mimics the Spemann organizer in dorsalizing Xenopus mesoderm. 1993, Pubmed , Xenbase
Stern, Head-tail patterning of the vertebrate embryo: one, two or many unresolved problems? 2006, Pubmed
Tour, Gbx2 interacts with Otx2 and patterns the anterior-posterior axis during gastrulation in Xenopus. 2002, Pubmed , Xenbase
Tucker, The BMP signaling gradient patterns dorsoventral tissues in a temporally progressive manner along the anteroposterior axis. 2008, Pubmed
von Bubnoff, The Xenopus laevis homeobox gene Xgbx-2 is an early marker of anteroposterior patterning in the ectoderm. 1996, Pubmed , Xenbase
Wacker, The initiation of Hox gene expression in Xenopus laevis is controlled by Brachyury and BMP-4. 2004, Pubmed , Xenbase
Wacker, Timed interactions between the Hox expressing non-organiser mesoderm and the Spemann organiser generate positional information during vertebrate gastrulation. 2004, Pubmed , Xenbase
Wellik, Hox10 and Hox11 genes are required to globally pattern the mammalian skeleton. 2003, Pubmed
Zhu, Collinear Hox-Hox interactions are involved in patterning the vertebrate anteroposterior (A-P) axis. 2017, Pubmed , Xenbase
Zimmerman, The Spemann organizer signal noggin binds and inactivates bone morphogenetic protein 4. 1996, Pubmed , Xenbase