A nodal signaling pathway regulates the laterality of neuroanatomical asymmetries in the zebrafish forebrain

Animals show behavioral asymmetries that are mediated by differences betwee n the left and right sides of the brain. We report that the laterality of a symmetric development of the diencephalic habenular nuclei and the photorec eptive pineal complex is regulated by the Nodal signaling pathway and by mi dline tissue. Analysis of zebrafish embryos with compromised Nodal signalin g reveals an early role for this pathway in the repression of asymmetricall y expressed genes in the diencephalon. Later signaling mediated by the EGF- CFC protein One-eyed pinhead and the forkhead transcription factor Schmalsp ur is required to overcome this repression. When expression of Nodal pathwa y genes is either absent or symmetrical, neuroanatomical asymmetries are st ill established but are randomized. This indicates that Nodal signaling is not required for asymmetric development per se but is essential to determin e the laterality of the asymmetry.