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Akiko Nishiyama glial cell biology I am interested in understanding how different cell types in the mammalian central nervous system (CNS) interact with each other. I have been studying a population of glial cells in the rodent CNS which can be identified by the expression of the NG2 proteoglycan. During development NG2 glial cells give rise to oligodendrocytes, which make myelin sheaths around axons. However, not all NG2 cells differentiate into oligodendrocytes, and a large number of NG2 glial progenitor cells persist in the mature CNS (see Figure). I first became aware of the importance of glial cells while I was a resident in neuropathology and was examining brain tissues from patients who had died of various neurodegenerative diseases. I learned that although nervous system dysfunction usually occurs as a result of neuronal damage, glial cells are the first cells to react to most types of injury, long before morphological changes in neurons become apparent. I wanted to be able to analyze the cellular responses to injury at the molecular level, beyond the morphological studies routinely carried out in a pathology laboratory, and received my graduate training in Molecular Neuropathology / Neurobiology at the Brain Research Institute in Niigata, Japan. While studying gene expression in different glial cell lines, I became interested in the heterogeneity of glial cells. This led me to seek postdoctoral training at the La Jolla Cancer Research Foundation with Bill Stallcup, who had just reported that the NG2 proteoglycan is expressed on a subpopulation of glial progenitor cells. While determining the primary structure and some biochemical properties of the rat NG2 proteoglycan as a part of a group studying cell adhesion molecules in development, I developed an interest in how extracellular and cell surface molecules play a role in regulating cell proliferation, migration, and differentiation. During the second half of my postdoctoral period, I studied the distribution of NG2 cells in the CNS and found that numerous NG2 cells exist not only in the developing brain but also in the mature brain. This observation led to the question of whether the NG2 cells in the adult CNS are a source of remyelinating cells in demyelinating lesions, which I pursued at the
Cleveland Clinic, where I was a part of a group studying various aspects of the demyelinating disease, multiple sclerosis. I joined this department in 1998. We are currently using the following approaches to study what NG2 cells do and how their proliferation and differentiation are regulated. 1) Use primary cultures of neurons and different glial cells to study the effects of glial cells on neuronal functions. 2) Study the interaction between NG2 cells and axons. 3) Study molecular mechanisms of NG2 cell proliferation and differentiation in dysmyelinating mutant mice and demyelinating lesions. 4) Use the BAC transgenic approach to target the expression of various genes to NG2 cells in transgenic mice to study the physiological functions of NG2 cells. 5) Use newly generated transgenic mouse lines to trace the fate of NG2 cells and examine whether NG2 cells can function as stem cells. Selected Publications Yang, Z., R. Suzuki, S. B. Daniels, C. B. Brunquell, C. J. Sala, A. Nishiyama. (2006). NG2 glial cells provide a favorable substrate for growing axons. J Neurosci. 26(14):3829-39, 2006. (featured in Journal Club: Barbara Lober. Role of NG2 in Development and Regeneration. J Neurosci. 26(27):7127-7128, 2006.) Ziskin J. L., A. Nishiyama, M. Fukuya, M. E. Rubio, D. E. Bergles. (2007). Vesicular release of glutamate from unmyelinated axons in white matter. Nature Neuroscience 10(3):321-30. Zhu, X., D. E. Bergles, A. Nishiyama. (2008). NG2 glial cells generate both oligodendrocytes and astrocytes. Development 135(1):145-57. Komitova, M., X. Zhu, D. R. Serwanski, and A. Nishiyama. (2009). NG2 cells are distinct from neurogenic cells in the subventricular zone. J Comp Neurol 512:702-715. Nishiyama, A., M. Komitova, R. Suzuki, X. Zhu. (2009). NG2 cells (polydendrocytes): multifunctional cells with lineage plasticity. Nature Rev Neurosci 10:9-22.
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Page 5 and 6: Graduate Program The Graduate Resea
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