The isthmic organizer (IsO) is a signalling centre that lies between, and patterns, the mesencephalon (mes) and rostral metencephalon (met) regions of the neural tube, which give rise to the midbrain and cerebellum, respectively. FGF8 and WNT1 are key components of the signalling activity of this centre,although their exact functions here remains unclear. To further investigate the role of FGF8 in the IsO, Gail Martin and colleagues conditionally inactivated Fgf8 in the midbrain/hindbrain region of mice. The progressive loss of FGF8 here resulted in a dose-dependent loss of tissue; by E17.5, the entire midbrain, isthmus and cerebellum were absent in mutant embryos (see ), owing to ectopic cell death in the progenitors of these structures. FGF8 is also required to maintain gene expression in this region,including that of Wnt1 and Gbx2. These findings highlight an essential role for FGF8 in regulating gene expression and cell survival in this region. Whether it also directly functions in the patterning of these tissues, as previously believed, remains to be resolved.
