Inhibition of BMP activity by the FGF signal promotes posterior neural development in zebrafish.
The expression patterns of region-specific neuroectodermal genes and fate-map analyses in zebrafish gastrulae suggest that posterior neural development is initiated by nonaxial signals, distinct from organizer-derived secreted bone morphogenetic protein (BMP) antagonists. This notion is further supported by the misexpression of a constitutively active form of zebrafish BMP type IA receptor (CA-BRIA) in the zebrafish embryos. It effectively suppressed the anterior neural marker, otx2, but not the posterior marker, hoxb1b. Furthermore, we demonstrated that the cells in the presumptive posterior neural region lose their neural fate only when CA-BRIA and Xenopus dominant-negative fibroblast growth factor (FGF) receptors (XFD) are coexpressed. The indications are that FGF signaling is involved in the formation of the posterior neural region, counteracting the BMP signaling pathway within the target cells. We then examined the functions of Fgf3 in posterior neural development. Zebrafish fgf3 is expressed in the correct place (dorsolateral margin) and at the correct time (late blastula to early gastrula stages), the same point that the most precocious posterior neural marker, hoxb1b, is first activated. Unlike other members of the FGF family, Fgf3 had little mesoderm-inducing activity. When ectopically expressed, Fgf3 expands the neural region with suppression of anterior neural fate. However, this effect was mediated by Chordino (zebrafish Chordin), because Fgf3 induces chordino expression in the epiblast and Fgf3-induced neural expansion was substantially suppressed in dino mutants with mutated chordino genes. The results obtained in the present study reveal multiple actions of the FGF signal on neural development: it antagonizes BMP signaling within posterior neural cells, induces the expression of secreted BMP antagonists, and suppresses anterior neural fate.
Koshida
Sumito
S
Division of Biological Science, Graduate School of Science, Nagoya, Chikusa-ku, 464-8602, Japan.
Shinya
Minori
M
Nikaido
Masataka
M
Ueno
Naoto
N
Schulte-Merker
Stefan
S
Kuroiwa
Atsushi
A
Takeda
Hiroyuki
H
D000818:Animals; D019521:Body Patterning / Q000187:drug effects; D055419:Bone Morphogenetic Protein 7; D052005:Bone Morphogenetic Protein Receptors, Type I; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors*; D003001:Cloning, Molecular; D004625:Embryo, Nonmammalian / Q000502:physiology; D051518:Fibroblast Growth Factor 3; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000494:pharmacology; D005775:Gastrula / Q000502:physiology; D009024:Morphogenesis / Q000235:genetics; D009420:Nervous System / Q000196:embryology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000494:pharmacology; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics; D017978:Receptors, Growth Factor / Q000235:genetics*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000502:physiology; D029867:Xenopus Proteins; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins
D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; C489198:FGF3 protein, Xenopus; D051518:Fibroblast Growth Factor 3; D011518:Proto-Oncogene Proteins; D017468:Receptors, Fibroblast Growth Factor; D017978:Receptors, Growth Factor; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; C525822:bmp7.1 protein, Xenopus; C525826:bmp7a protein, zebrafish; C489200:fgf3 protein, zebrafish; D005346:Fibroblast Growth Factors; D017346:Protein Serine-Threonine Kinases; D052005:Bone Morphogenetic Protein Receptors, Type I