title: Fgf signalling controls the dorsoventral patterning of the zebrafish embryo.
abstract: The establishment of dorsoventral (DV) patterning in vertebrate embryos depends on the morphogenic activity of a group of Tgfbeta superfamily members, the bone morphogenetic proteins (Bmps) (which specify ventral cell fates), and on their interaction with their dorsally secreted cognate inhibitors chordin and noggin. In the zebrafish, genetic analysis has revealed that Bmp2b and Bmp7, as well as their antagonist chordin, are required for proper DV patterning. The expression of Bmp genes is initially activated in the whole blastula. Well before the beginning of gastrulation, Bmp gene expression progressively disappears from the dorsal side to become restricted to the ventral part of the embryo. We show that this early restriction of Bmp gene expression, which occurs independently of noggin and chordin, is an essential step in the establishment of DV patterning. The progressive ventral restriction of Bmp gene transcripts is coincident with the spreading of Fgf activity from the dorsal side of the embryo, suggesting that Fgf signalling is implicated in dorsal downregulation of Bmp gene expression. In accordance with this, activation of the Fgf/Ras/Mapk-signalling pathway inhibits ventral Bmp gene expression, thereby causing a dorsalisation of the embryo. Conversely, inhibition of Fgf signalling causes Bmp gene expression to expand dorsally, leading to an expansion of ventral cell fates. In accordance with an important role of Fgf signalling in the DV patterning of the zebrafish, we show that loss of Fgf8 function enhances the ventralisation of chordin-deficient embryos. Our results thereby demonstrate that pre-gastrula stage Fgf-signalling is essential to delimit the expression domain of the genes encoding the functional morphogen of the dorsoventral axis of the early zebrafish embryo.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, UMR 7104, CNRS/INSERM/ULP, 1 rue Laurent Fries, BP10142, CU de Strasbourg, 67404, Illkirch Cedex, France.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Fürthauer
authors.forename: Jeanne
authors.initials: J
authors.lastname: Van Celst
authors.forename: Christine
authors.initials: C
authors.lastname: Thisse
authors.forename: Bernard
authors.initials: B
authors.lastname: Thisse
mesh_terms: D000818:Animals; D001757:Blastomeres / Q000166:cytology / Q000502:physiology; D019521:Body Patterning / Q000502:physiology*; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000502:physiology; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000502:physiology; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D009024:Morphogenesis; D009924:Organ Culture Techniques; D015398:Signal Transduction; D014158:Transcription, Genetic / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000235:genetics
chemical_list: D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta; D029961:Zebrafish Proteins; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors