Fgf signalling through MAPK cascade is required for development of the subpallial telencephalon in zebrafish embryos

The telencephalon is formed in the most anterior part of the central nervou s system (CNS) and is organised into ventral subpallial and dorsal pallial domains. In mice, it has been demonstrated that Fgf signalling has an impor tant role in induction and patterning of the telencephalon. However, the pr ecise role of Fgf signalling is still unclear, owing to overlapping functio ns of Fgf family genes. To address this, we have examined, in zebrafish emb ryos, the activation of Ras/mitogen-activated protein kinase (MAPK), one of the major downstream targets of Fgf signalling. Immunohistochemical analys is reveals that an extracellular signal-regulated kinase (ERK), a vertebrat e MAPK is activated in the anterior neural boundary (ANB) of the developing CNS at early segmentation stages. Experiments with Fgf inhibitors reveal t hat ERK activation at this stage is totally dependent on Fgf signalling. In terestingly, a substantial amount of ERK activation is observed in ace muta nts in which fgf8 gene is mutated. We then examine the function of Fgf sign alling in telencephalic development by use of several inhibitors to Fgf sig nalling cascade, including dominant-negative forms of Ras (Ras(N17)) and th e Fgf receptor (Fgfr), and a chemical inhibitor of Fgfr, SU5402. In treated embryos, the induction of telencephalic territory normally proceeded but t he development of the subpallial telencephalon was suppressed, indicating t hat Fgf signalling is required for the regionalisation within the telenceph alon. Finally, antisense experiments with morpholino-modified oligonucleoti des suggest that zebrafish fgf3, which is also expressed in the ANB, cooper ates with fg8 in subpallial development.