Extracellular matrix and cellular motility

E-mail: gellerh@nhlbi.nih.gov

Office: Building 10, Room 8C213

• Molecules that control development and regeneration in the nervous system

Both development of the neuron and the neuronal response to injury are shaped by interactions between neurons and glial cells. Glia make soluble molecules and substrate-bound molecules that shape neuronal growth. Current research focuses on the role of astrocytes and Schwann cells, the major glial cell in the central and peripheral nervous system, respectively. Astrocytes normally provide a favorable environment for neurons, e.g., during development they promote neuronal migration and process outgrowth. However, in certain circumstances, such as after injury,astrocytes are inhibitory and are a major part of the "glial scar" that forms around the injury site. When severed neurons growing on Schwann cells encounter astrocytes, they change their direction of growth. Thus, Schwann Cell/Astrocyte interactions after injury form a boundary. Identifying the specific gene products that are responsible for the permissive or inhibitory actions of astrocytes as well as their mechanism of action is a major effort underway in this laboratory. Many of these molecules reside within the extracellular matrix, where growing neurons will encounter them. Some molecules are permissive for growth and guidance, while other molecules are inhibitory. We believe that repair of the injured nervous system will be increased by harnessing the permissive cues, and blocking the inhibitory ones. The ultimate goal is to promote neuronal regeneration by preventing these changes in astrocytes, adding permissive molecules to astrocytes, or causing neurons to ignore the inhibitory cues.