Does the isthmic organizer influence D/V patterning of the midbrain?

Early brain and spinal cord regionalization along the dorsoventral axis are thought to be governed by similar mechanisms. Subsequently, the size of the alar plate of the neural tube increases dramatically in the midbrain and anterior forebrain, compared to the spinal cord. This suggests that additional mechanisms may be required to refine A/P and D/V patterning in these structures. The isthmic organizer is a signaling center that controls both growth and patterning in the midbrain and anterior hindbrain through the production of several secreted molecules, in particular FGF8. Several studies have indicated that the isthmic organizer is involved in the positioning and development of the midbrain roof and floor plates, the two structures that respectively mark the dorsal and ventral axis of the neural tube. It remains unclear whether its influence on axis formation in the midbrain is a consequence of a more general function of the isthmic organizer/FGF8 as a modulator of DV patterning or if selection of an axis is a necessary and general by-product of its organizing function not directly related to D/V patterning. In this paper, we review the current data supporting each possibility.