1. Cells in the central nervous system – NG2 cells. We study a glial cell population called NG2 cells (also known as polydendrocytes or oligodendrocyte precursor cells). Research projects in the lab include identifying mechanisms that regulate their self-renewal versus differentiation and elucidating their role in the neural circuit.
2. Distribution and morphology of NG2 cells in the adult rat brain. NG2 cells can be visualized by using antibodies to the NG2 protein (cartoon on the right). NG2 cells constitute 2-9% of the total brain cells and are uniformly distributed throughout the CNS. They have many slender processes through which they interact with other cell types.
3. NG2DsRed BAC transgenic mice. We have generated several transgenic mouse lines to study the fate and function of NG2 cells. In NG2DsRed mice, DsRed fluorescence is seen in NG2 cells and can be used to visualize NG2 cells in vivo.
4. Genetic fate mapping of NG2 cells We can follow the fate of NG2 cells using the cre-loxP technology. This uses site-specific recombination to permanently induce the expression of a reporter gene that can be used to track the fate of NG2 cells after the cells downregulate NG2 expression and differentiate into other cell types.
5. The fate of NG2 cells . Through genetic fate mapping and other methods, we now know that NG2 cells throughout all developmental stages give rise to oligodendrocytes. In addition, a subpopulation of NG2 cells in the prenatal CNS generate protoplasmic astrocytes in the ventral gray matter. We do not think NG2 cells contribute significantly to the neuronal population under normal physiological conditions.
6. Experimental approaches used in our lab. We use a variety of experimental approaches ranging from whole animal studies and tissue analyses to cell culture, biochemical, and molecular genetic methods. For tissue analyses, we use immunofluorescence and confocal microscopy, super resolution microscopy, and electron microscopy.
Research in our lab
Overview
NG2 cells (also known as polydendrocytes or oligodendrocyte precursor cells) represent a resident glial cell population in the mammalian central nervous system (CNS). Their most well characterized function is to generate oligodendrocytes which produce myelin sheaths around axons and precisely regulate the timing of signal arrival. We are interested in understanding the basic biological principles that dictate the cellular behavior NG2 cells and how NG2 cells interact with the other cellular constituents of the CNS to modulate various physiological processes.
Current research focus
- Molecular and cellular mechanisms that regulate the density and lineage plasticity of NG2 cells under physiological and pathological conditions.
- How NG2 cells communicate with neurons and other cell types in the CNS.
- The role of NG2 cells in the neural circuit, particularly in understanding whether there are functions of NG2 cells that are independent of their role as oligodendrocyte precursor cells.
We are using a wide variety of approaches to answer these questions. Common approaches used in the lab include mouse genetics combined with immunohistochemistry, tissue culture (dissociated and organotypic), fluorescence and confocal microscopy, and biochemical and molecular biological / molecular genetic analyses. We are also expanding our analyses to include whole animal studies such as behavioral analyses of mutant mice. Other methods that we are incorporating into our studies include super resolution microscopy and whole genome profiling of transcripts and chromatin modifications.
Past contributions
We have continuously made progress toward understanding the biology of NG2 cells over the past 25 years.
1990s - We have applied immunodetection of two proteins, NG2 and platelet-derived growth factor receptor alpha (Pdgfra) to define a population of glial cells in the mammalian central nervous system (CNS). NG2 cells exist not only in the developing CNS but also are distributed uniformly throughout the mature CNS where they exhibit a complex multi-processed morphology and remain proliferative throughout life. They are distinct from neurons, astrocytes, microglia, or mature oligodendrocytes.
2000s - There were questions about whether NG2 indeed give rise to oligodendrocytes that make myelin sheaths or whether that also serve as precursors to other cell types. To solve this question, we generated transgenic mouse lines to fate map NG2 cells at different developmental stages. NG2 cells in the postnatal brain are restricted to the oligodendrocyte lineage and those in the adult brain continue to produce myelinating oligodendrocytes. In addition, a subpopulation of NG2 cells in the prenatal CNS produce about one-third of the astrocytes in certain gray matter regions but not in the white matter.
Lab Contact
Phone:
860-486-1694
Location:
Pharmacy/Biology Building (PBB)
613, 617, 618