Insight: Research Edition

Fall 2005

Migration Studies Help Researchers Understand Brain Structures

When we think of migration, we often imagine birds flying thousands of miles south to escape winter’s cold, salmon swimming upstream to spawn and die, or massive caribou herds heading across the tundra to bear their young. We don’t often think of migration in terms of human cells, with migratory distances measured in microns, not miles. But the migration of cells – particularly neuronal cells – is critically important to the normal functioning of the human nervous system.

An extreme example of this is Kallman’s syndrome with symptoms including gonadotrophin releasing hormone (GnRH) deficiency and accompanying effects, and a diminished or non-existent sense of smell. Kallman’s syndrome arises when GnRH secreting neurons in a developing fetus fail to migrate from their site of origin in the nose into the basal forebrain. The syndrome is usually inherited and, for some forms, affects more males than females

Kallman’s syndrome, Prader-Willi and Rubenstein-Taybi are all rare genetic conditions that affect neuroendocrine structures. While unknown to most of us, these conditions are an area of interest to Dr. Stuart Tobet, an Associate Professor in the Department of Biomedical Sciences and a member of the Program in Molecular, Cellular and Integrative Neurosciences. Dr. Tobet’s laboratory is examining how multiple signal types affect migration and cell position in the developing nervous system, and is using innovative tracking systems and video microscopy to image these migrations.

“Neurons form communities from which they can gather information and communicate about their environments,” said Dr. Tobet. “Our brains evolved with the ability to compartmentalize and have cell groups that integrate and carry out different functions. We are studying the migration of cells into groups and what affects their movements. Differences between the two sexes in how functions are carried out, and in the ability to protect and recover from internal and external assaults including strokes and brain injury that occur during development, are areas of interest for the laboratory. There are differences in neuronal function between the two sexes that are above and beyond the more commonly thought of differences due to hormones.”

Dr. Tobet’s laboratory is using the ventromedial nucleus of the hypothalamus (VMH) and the proptic area as model systems for his group’s research. These regions are critical components of the brain regulating homeostatic, neuroendocrine and behavioral functions. Cells in these regions migrate to specific positions according to the chemical environment around them, the types of neighboring cells, and potential anatomical connections. In his research, Dr. Tobet is able to follow the formation of nuclei in vitro using video microscopy – very elaborate home movies of cells on the move.

It takes many investigators to carry out modern-day neuroscience research and Dr. Tobet’s collaborations stretch from Oregon on the West Coast to Boston and Virginia on the East Coast and includes Colorado, Texas and Kansas in between. Recently, Dr. Tobet was joined in his research efforts by Dr. Gregor Majdic, Assistant Professor, Department of Veterinary Faculty, Center for Animal Genomics, at the University of Ljubljana in Slovenia. Earlier this year, Colorado State University and the University of Ljubljana formalized their relationship with a Memorandum of Understanding that will allow the two laboratories to work together in a way that will improve cooperation and speed up progress in studies of hormone-independent sex differences in the brain.

“Research into the workings of the brain is exceptionally challenging, so working with Dr. Majdic in a team effort means we can meet the challenges more creatively and with better results,” said Dr. Tobet. “The more we learn the better we are able to put some of the pieces together, and the greater our understanding of ourselves.”

To view video images of cellular migrations in a mouse model, go to www.cvmbs.colostate.edu/bms/tobet.htm.