TY - JOUR
T1 - Inhibition of BMP activity by the FGF signal promotes posterior neural development in zebrafish
AU - Koshida, Sumito
AU - Shinya, Minori
AU - Nikaido, Masataka
AU - Ueno, Naoto
AU - Schulte-Merker, Stefan
AU - Kuroiwa, Atsushi
AU - Takeda, Hiroyuki
N1 - Funding Information:
We thank Dr. I. Dawid for his critical reading of the manuscript. We also thank Drs. M. Mishina and H. Mori for providing zebrafish otx2 cDNA, Dr. T. Jowett for zebrafish krox20 cDNA, Dr. J.-S. Joly for eve-1, Dr. N. Holder for hoxa-1 cDNA, Dr. M. Kobayashi for six3, Dr. E. Amaya for XFD and HAVnot cDNA, Drs. M. Fürthauer and B. Thisse for zebrafish fgf8 cDNA, Dr. M. Furutani-Seiki for zebrafish dino mutant, and Mr. T. Tanaka for his contribution to the initial part of this study. This work was supported in part by CREST (Core Research for Evolutionary Science and Technology) of the Japan Science and Technology Corporation (JST), by a Bio-Design Project and Pioneering Research Project in Biotechnology from the Ministry of Agriculture, Forestry and Fisheries of Japan, and by grants-in-aids from the Ministry of Education, Science, and Culture of Japan.
PY - 2002/4/1
Y1 - 2002/4/1
N2 - 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.
AB - 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.
KW - BMP
KW - Chordin
KW - FGF
KW - Marginal mesoderm
KW - Neural induction
KW - Organizer
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U2 - 10.1006/dbio.2002.0581
DO - 10.1006/dbio.2002.0581
M3 - Article
C2 - 11900455
AN - SCOPUS:0036534583
VL - 244
SP - 9
EP - 20
JO - Developmental Biology
JF - Developmental Biology
SN - 0012-1606
IS - 1
ER -