The development of left-right differences in the brain is a prominent feature of the human brain. The importance of such left-right differences is evidenced by the psychiatric and learning disorders linked to congenital defects in forebrain asymmetry, including schizophrenia, depression and dyslexia. However, it is difficult to study the way in which asymmetry arise prior to adulthood. Because left-right differences in the brain are found throughout the vertebrate lineage, it is possible to use a model organism to address the question of how asymmetric brain development occurs. For such studies, we have chosen the zebrafish, because of the molecular, genetic, and embryological tools available, and because there is prominent asymmetry in a region of the forebrain called the epithalamus. We have isolated and cloned two mutations which cause the normally asymmetric epithalamus to develop symmetrically instead, and are now studying when and how the mutated genes act in forming left-right differences in the brain. In addition, we are investigating a family of molecules, called potassium channel tetramerization domain (KCTD) proteins, which are asymmetrically expressed in the zebrafish epithalamus.