The role of Fyn tyrosine kinase in oligodendrocyte development and myelination.

Format:

Book

Thesis/Dissertation

Author/Creator:

Sperber, Brian Robert.

Contributor:

McMorris, F. Arthur, advisor.

University of Pennsylvania.

Language:

English

Subjects (All):

Developmental biology.

Neurosciences.

0317.

0758.

Penn dissertations--Neuroscience.

Neuroscience--Penn dissertations.

Local Subjects:

Penn dissertations--Neuroscience.

Neuroscience--Penn dissertations.

0317.

0758.

Physical Description:

185 pages

Contained In:

Dissertation Abstracts International 61-06B.

System Details:

Mode of access: World Wide Web.

text file

Summary:

Fyn, a member of the Src family of non-receptor protein tyrosine kinases, is highly expressed in the brain and has been suggested to play an important role in the developing central nervous system (CNS). Recent studies indicate that Fyn is important for normal myelination, but there are still many unanswered questions. In this thesis, I analyzed myelination and oligodendrocyte development in mice that lack detectable Fyn protein (fyn--/-- mice).

I found a significant myelin deficit in fyn--/-- mouse forebrain, but not spinal cord. The myelin deficit in forebrain was most severe at one month of age and persisted beyond one year of age. Myelin content in src--/-- mice, yes--/-- mice, and lyn --/-- mice was normal; thus, Fyn is unique among Src-family kinases in that it is required for normal myelination. Analysis of fyn--/-- mouse spinal cord and corpus callosum revealed a normal number of oligodendrocytes in the spinal cord, but a reduced number in corpus callosum. In all areas studied, myelin that was present in fyn--/-- mice was morphologically normal. The number of myelinated fibers appeared normal in spinal cord and optic nerve from fyn--/-- mice; in contrast, the number of myelinated fibers in the fyn--/-- corpus callosum was significantly reduced at one month of age. Therefore, the fyn--/-- hypomyelination phenotype was restricted to brain and was due to reduced numbers of oligodendrocytes and myelinated fibers. Finally, I investigated myelin content in mice expressing a catalytically-inactive full-length form of Fyn. These mice were also significantly myelin deficient at one month of age, indicating that the kinase activity of Fyn is essential for normal myelination.

To determine whether Fyn is necessary for normal oligodendrocyte development, I analyzed the development of oligodendrocytes in neuron-free glial cell cultures from fyn--/-- mice. I demonstrated that fyn--/-- oligodendrocytes developed to the stage where they elaborate an extensive network of processes and express the antigenic components of mature oligodendrocytes. However, I observed fewer oligodendroglia in fyn--/-- cultures and a reduced number of morphologically mature cells. In addition, I found that, unlike in wild-type cells, insulin-like growth factor failed to stimulate morphological development in fyn--/-- oligodendroglia.

Notes:

Thesis (Ph.D. in Neuroscience) -- University of Pennsylvania, 2000.

Source: Dissertation Abstracts International, Volume: 61-06, Section: B, page: 2971.

Supervisor: F. Arthur McMorris.

Local Notes:

School code: 0175.

ISBN:

9780599821927

Access Restriction:

Restricted for use by site license.