Studies on the role of fibroblast growth factor signaling in neurogenesis using conjugated/aged animal caps and dorsal ectoderm-grafted embryos.
Basic fibroblast growth factor (bFGF) has been shown to induce neural fate in dissociated animal cap (AC) cells or in AC explants cultured in low calcium and magnesium concentrations. However, long-term disclosure of the cap may cause diffusion of the secreted molecule bone morphogenetic protein 4 (BMP-4), a neural inhibitor present in the AC. This may contribute to the subsequent neurogenesis induced by bFGF. Here we used conjugated and aged blastula AC to avoid diffusion of endogenous molecules from the AC. Unlike noggin, bFGF failed to induce neural tissue in this system. However, it enhanced neuralization elicited by a dominant negative BMP receptor (DN-BR) that inhibits the BMP-4 signaling. Posterior neural markers were turned on by bFGF in AC expressing DN-BR or chordin. Blocking the endogenous FGF signal with a dominant negative FGF receptor (XFD) mainly inhibited development of posterior neural tissue in neuralized ACs. These in vitro studies were confirmed in vivo in embryos grafted with XFD-expressing ACs in the place of neuroectoderm. Expression of some regional neural markers was inhibited, although markers for muscle and posterior notochord were still detectable in the grafted embryos, suggesting that XFD specifically affected neurogenesis but not the dorsal mesoderm. The use of these in vitro and in vivo model systems provides new evidence that FGF, although unable to initiate neurogenesis on its own, is required for neural induction as well as for posteriorization.
Xu
R H
RH
Intramural Research Support Program, Science Applications International Corporation-Frederick, Frederick, Maryland 21702-1201, USA.
Kim
J
J
Taira
M
M
Sredni
D
D
Kung
H
H
D000818:Animals; D055415:Bone Morphogenetic Protein 4; D052004:Bone Morphogenetic Protein Receptors; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002490:Central Nervous System / Q000196:embryology; D004475:Ectoderm / Q000502:physiology; D047108:Embryonic Development; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D009432:Neural Crest / Q000196:embryology*; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors; D017978:Receptors, Growth Factor; D015398:Signal Transduction; D029867:Xenopus Proteins; D014982:Xenopus laevis
D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor; D017978:Receptors, Growth Factor; D029867:Xenopus Proteins; C525812:bmp4 protein, Xenopus; D016222:Fibroblast Growth Factor 2; D052004:Bone Morphogenetic Protein Receptors