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Neural stem cells (green) in the adult brain.
 
Grigori Enikolopov
Associate Professor
Ph.D., Institute of Molecular Biology,
USSR Academy of Sciences, Moscow, 1978

Stem cells; neurogenesis; development; signal transduction

email enikolop@cshl.edu, phone (516) 367-8316 , fax (516) 367-6805

Stem cells have a unique ability to self renew and to produce progenitor cells that eventually generate differentiated cells. This cascade of transitions from stem cells to their differentiated progeny is under dynamic control, ensuring a rapid response to demands for more cells due to stress, damage, or altered environment. We use flies, frogs, and mice as models to study signals that regulate distinct steps in the differentiation cascade and mediate interactions between stem cells and their microenvironment.

Our focus is on stem cells in the adult brain and the relationship between neurogenesis and mood disorders. We have generated several models to study how stem cells give rise to progenitors and, ultimately, to neurons. We are using these models to determine the targets of antidepressant therapies, to identify signaling pathways that control generation of new neurons in the brain, and to search for neuronal and neuroendocrine circuits involved in mood regulation.

Much of our interest is related to a versatile signaling molecule, nitric oxide (NO). We found that NO suppresses cell division, helping to control the balance between proliferation and differentiation. It acts as a negative regulator of cell division in the developing and adult nervous system, such that by manipulating NO levels we can change the number of neural stem and progenitor cells. Our findings define NO as an essential negative regulator of cell proliferation in the differentiation cascade. We are working to dissect the interactions between NO and the signaling pathways that control stem cell division and differentiation.

Selected Publications

Gleiberman, A.S., Michurina, T., Encinas, J.M., Roig, J.L., Krasnov, P., Balordi, F., Fishell, G., Rosenfeld, M.G., and Enikolopov, G. 2008. Genetic approaches identify adult pituitary stem cells. Proc. Nat. Acad. Sci. USA, 105: 6332-6337.

Encinas, J.M., Vaahtokari, A., and Enikolopov, G. 2006. Fluoxetine targets early progenitor cells in the adult brain. Proc. Natl. Acad. Sci. USA 103: 8233–8238.

Stasiv, Y., Kuzin, B., Regulski, M., Tully, T., and Enikolopov, G. 2004. Regulation of multimers via truncated isoforms: a novel mechanism to control nitric oxide signaling. Genes Dev. 18: 1812–1823.

Kuzin, B., Roberts, I., Peunova, N., and Enikolopov, G. 1996. Nitric oxide regulates cell proliferation during Drosophila development. Cell 87: 639–649.

Peunova, N. and Enikolopov, G. 1995. Nitric oxide triggers a switch to growth arrest during differentiation of neuronal cells. Nature 375: 68–73.




Cold Spring Harbor Laboratory