FGF signaling and the anterior neural induction in Xenopus

We previously showed that FGF was capable of inducing Xenopus gastrula ecto derm cells in culture to express position-specific neural markers along the anteroposterior axis in a dose-dependent manner. However, conflicting resu lts have been obtained concerning involvement of FGF signaling in the anter ior neural induction in vivo using the same dominant-negative construct of Xenopus FGF receptor type-1 (Delta XFGFR-1 or XFD). We explored this issue by employing a similar construct of receptor type-4a (XFGFR-4a) in addition , since expression of XFGFR-4a was seen to peak between gastrula and neurul a stages, when the neural induction and patterning take place, whereas expr ession of XFGFR-1 had not a distinct peak during that period. Further, thes e two FGFRs are most distantly related in amino acid sequence in the Xenopu s FGFR family. When we injected mRNA of a dominant-negative version of XFGF R-4a (Delta XFGFR-4a) into eight animal pole blastomeres at 32-cell stage, anterior defects including loss of normal structure in telencephalon and ey e regions became prominent as examined morphologically or by in situ hybrid ization. Overexpression of Delta XFGFR-1 appeared far less effective than t hat of Delta XFGFR-4a. Requirement of FGF signaling in ectoderm for anterio r neural development was further confirmed in culture: when ectoderm cells that were overexpressing Delta XFGFR-4a were cocultured with intact organiz er cells from either early or late gastrula embryos, expression of anterior and posterior neural markers was inhibited, respectively. We also showed t hat autonomous neuralization of the anterior-type observed in ectoderm cell s that were subjected to prolonged dissociation was strongly suppressed by Delta XFGFR-4a, but not as much by Delta XFGFR-1. It is thus indicated that FGF signaling in ectoderm, mainly through XFGFR-4, is required for the ant erior neural induction by organizer. We may reconcile our data to the curre nt "neural default model," which features the central roles of BMP I signal ing in ectoderm and BMP4 antagonists from organizer, simply postulating tha t the neural default pathway in ectoderm includes constitutive FGF signalin g step. (C) 1999 Academic Press.