Molecular approaches to cerebral laterality: development and neurodegeneration

Little is understood about the genetic or epigenetic mechanisms that underlie brain asymmetry. Because higher cognitive functions such as language, constructional and spatial abilities, and attention are organized along the left/right axis, understanding the underpinnings of this process has significant implications for both developmental biology and cognitive neuroscience. However, scientists have begun to explore, in only the most preliminary manner, the influences of subtle biologically inherited brain asymmetries on human behavior and disease. Because brain asymmetry develops prenatally, the recognition of asymmetry in neurodegeneration implies a possible relationship between the development of cerebral laterality and regional vulnerability in neurodegenerative diseases. This suggests that the study of cerebral asymmetry and laterality is likely to be relevant to a number of degenerative conditions that were previously considered to be only diseases of aging. In this article, I will outline our perspective and some of the approaches that my laboratory has begun to take to characterize the molecular basis of cerebral asymmetry. Most of these data are preliminary and the models presented are highly speculative, reflecting the primitive stage of work defining the molecular basis of cerebral asymmetry.