Early requirement for fgf8 function during hindbrain pattern formation in zebrafish

Fibroblast growth factor (FGF) signaling is required for normal development of the vertebrate brain, including the isthmus and caudal regions of the hindbrain. Recent work in zebrafish has identified a requirement for the combination of fgf3 and fgf8 functions in specification of rhombomeres 5 and 6 (r5, r6), when evaluated at mid- and late somitogenesis stages. However, when examined earlier in development, during early somitogenesis stages, FGF8 alone is required to initiate r5 and r6 development. Both a mutation in fgf8 and injection of fgf8-targeted antisense morpholino-modified oligonucleotides result in suppression of genes normally expressed in r5 and r6 by the one- to two-somite stage. This expression recovers by the six-somite stage, and we propose that this recovery is a response to activation of fgf3 and to delayed accumulation of fgf8. These data demonstrate an early, nonredundant requirement for fgf8 function in hindbrain patterning.