RESEARCH PROPOSAL GENE EXPRESSION, MECHANISMS OF CEREBRAL LATERALIZATION, AND SHARED CAUSATION OF DIVERSE BRAIN DISORDERS Elkhonon Goldberg, Department of Neurology, NYU School of Medicine; Dolores Malaspina, Department of Psychiatry, NYU School of Medicine; Tao Sun, Department of Cell and Developmental Biology, Cornell University Weill Medical College; Michal Harciarek, Department of Psychology, University of Gdansk, Poland. OBJECTIVE. Hemispheric lateralization is among the main architectural features of the mammalian brain but its genetic control is not fully understood. We propose that the aberrant expression of the genes controlling cerebral lateralization is central to the causation of several major brain disorders. Traditional taxonomies of neurological and neuropsychiatric disorders are outdated and stymie rather than facilitate the understanding of the basic mechanisms of major diseases. We propose to explore the common underlying causes of two major disorders that have been traditionally approached in an isolated, disconnected way: schizophrenia (Sch) and fronto-temporal dementia (FTD). This will be accomplished through advancing our understanding of the genetic control over hemispheric lateralization in the normal and abnormal brain. RATIONALE. The rationale for hypothesizing their shared causation and mechanisms lies in many common features including neuroanatomical similarities: in both Sch and FTD prefrontal (especially orbitofrontal) and temporal (especially anterior temporal) cortical regions are particularly implicated, mostly in the left hemisphere. HYPOTHESES. Cortical development is regulated by a number of genes, some of which are characterized by distinctly asymmetric gradients of expression: left-right and rostro-caudal. We hypothesize that: 1) Hemispheric lateralization is driven by a set of distinct, asymmetrically expressed genes 2) Aberrations of such asymmetrically expressed genes play a role in Sch and FTD, but at