Behavior of Schwann Cells in Diseases

Ling Niu
Department of Neurobiology
Stanford University School of Medicine
December 2001

My research is to use a combination of cell biology, biochemistry and molecular biology methods to study myelination. Myelination is a process that Schwann cells (a type of supporting cells in the nervous system) spread out their plasma membrane and spiral around nerve fiber a number of times to form a layer of coat called myelin. This line of research will increase our understanding of underlying mechanisms of some human diseases.

Myelin functions as an insulator to increase the speed of transmitting signals in the nervous system. If neural cells lose the myelin, human diseases occur. For example, the most common human peripheral disorder, Charcot-Marie-Tooth type1A (CMT1A) diseases, is due to the loss of myelin. These diseases affect one in every 2500 people, and are characterized by progressive muscle weakness, impaired gait, and loss of sensation.

CMT1A diseases are caused by mutations in the gene of peripheral myelin protein 22kDa (PMP22), one of the major protein components of myelin. Our lab focuses on a PMP22 point mutation called Trembler-J (TrJ). The TrJ nerves have shorter and thinner myelin segments compared to those of normal nerves. My research goal is to understand why this is so.

I use a co-culture system to observe the myelination process under the microscope. The co-culture system is a technique by which one can grow Schwann cells and nerve fibers in the same culture, and manipulate cell behavior such as myelination with certain drugs and chemicals. Because it is an in vitro system, real time observation of the myelination process is possible.

The Schwann cell starts myelinating by covering a certain length on the fiber and then increasing the myelin segment length by extending its membrane laterally from both ends along the fiber. During this process, some Schwann cells are pushed out of the axon to give more space to the remaining ones. Therefore, there are two possible explanations for shorter myelin segment formation of TrJ nerves: (1) the TrJ Schwann cells start with a shorter domain on the axon than the normal cells do; (2) the TrJ Schwann cell ability to extend is impaired. The co-culture system allows me to test these hypotheses by measuring the length of TrJ myelin segments at various time points during myelination.

Using the co-culture system we could also study many other issues (e.g., Schwann cell dividing, cell death, myelin protein expression regulation, etc.) to disclose the mechanisms of the TrJ mutation-associated myelin loss in the nervous system. Furthermore, we could test many factors and drugs for their ability to improve myelination in the TrJ Schwann cell co-culture. Findings from these studies have implications for improving treatment for CMT1A diseases.