The cerebral hemispheres are connected by the largest axonal tract in the mammalian brain: the corpus callosum (CC). During CC development, axons from one hemisphere navigate across the midline, channelled along their way by guidepost cells that secrete guidance cues, to reach specific targets on the other hemisphere. Neurofibromatosis type 2 (Nf2/Merlin) mouse mutants show a complete absence of the CC but how Nf2, a signalling protein involved in various cellular processes and signalling pathways, controls axonal pathfinding is currently unclear. Using Nf2-conditional knockout mouse models, Xinwei Cao and colleagues show that, surprisingly, Nf2 is not required in callosal neurons or their progenitors but is required in midline neural progenitors that generate guidepost cells (see p. ). The authors reveal that Nf2 controls guidepost development and the expression of Slit2, a major signalling cue secreted by guidepost cells, through the suppression of YAP, an effector of the Hippo pathway. These findings represent an exciting step forward in the molecular understanding of midline formation and brain wiring, as well as uncovering an intriguing previously undescribed function for the Hippo pathway.
