Laterotopic representation of left-right information onto the dorso-ventral axis of a zebrafish midbrain target nucleus

The habenulae are part of an evolutionarily highly conserved limbic-system conduction pathway that connects telencephalic nuclei to the interpeduncular nucleus (IPN) of the midbrain [1]. In zebrafish, unilateral activation of the Nodal signaling pathway in the left brain specifies the laterality of the asymmetry of habenular size [2-5]. We show "laterotopy" in the habenulo-interpeduncular projection in zebrafish, i.e., the stereotypic, topographic projection of left-sided habenular axons to the dorsal region of the IPN and of right-sided habenular axons to the ventral IPN. This asymmetric projection is accounted for by a prominent left-right (LR) difference in the size ratio of the medial and lateral habenular sub-nuclei, each of which specifically projects either to ventral or dorsal IPN targets. Asymmetric Nodal signaling directs the orientation of laterotopy but is dispensable for the establishment of laterotopy itself. Our results reveal a mechanism by which information distributed between left and right sides of the brain can be transmitted bilaterally without loss of LR coding, which may play a crucial role in functional lateralization of the vertebrate brain [6, 7].