| Faculty
Profile |
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Richard
S. Nowakowski, Ph.D
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Professor Department
of Neuroscience and Cell Biology New Jersey Professor of Spinal Cord Research BA 1971,
Wisconsin |
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UMDNJ lab: (732)
235-4647 |
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| Research Interests | Research Techniques | |
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Cell proliferation and migration during the development of the mammalian central nervous system. |
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Research Summary |
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During the development of the vertebrate CNS cell proliferation occurs, for the most part, in specialized proliferative zones that line the lateral ventricles. In this laboratory we are investigating the behavior of the cells that comprise these proliferative zones with an emphasis on understanding the output of the proliferative zones. Cell production in the cerebral cortex occurs over a period of time that extends over several days (or, in some species, weeks), resulting in the set of "postmitotic" cells, both neurons and glia, that comprise the adult nervous system. As development proceeds, the output of the proliferative zones varies in both cell number and cell class. Using the S-phase labels tritiated thymidine, bromodexoxyuridine and iododeoxyuridine (singly and in combination) we have documented changes in the length of the cell cycle and regional and microheterogeneity in the distribution of the proliferating population in phases of the cell cycle, and we have correlated changes in the direction and rate movements of cell nuclei with phases of the cell cycle. Recently, we have determined that during the 6 day neuronogenetic period of the mouse that there are 11 cell cycles that lengthen from about 8 hours on E11 to about 20 hours on E16. In addition, we have determined that the proportion of daughter cells that leave the proliferative populations (the Q-fraction) as opposed to those that re-enter the proliferative populations (the P-fraction) increases systematically during these 11 cell cycles. The principle that there is an increase in Q has provided considerable insight into the mechanisms of cortical development. For example, we have been able to calculate the number of founder cells in mouse at the onset of neuronogenesis and the relative expansion of the average proliferating cell. This idea has been extended to other species, particularly to primates, and represents a new way to think about the evolution of the CNS. |
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Key References |
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| For complete list: PubMed Tarui, T., Takahashi, T., Nowakowski, R.S., Hayes, N.L., Bhide, P.G., and V.S. Caviness, Jr., (2005) Overexpression of p27Kip1 alters laminar fate of neocortical neurons by altering probability of cell cycle exit. Cerebral Cortex, Available on-line on 1/12/2005. Sekiguchi, M., Takagi, K, Takagi, N., Date, I., Takeo, S., Tanaka, O., Yamato, I., Kobashikawa, S., Kojun Torigoe, K. and R.S. Nowakowski (2005). Time course and sequence of pathological changes in the cerebellum of microsphere-embolized rats. Exp. Neurol., 191: 266-275. Sekiguchi, M., Y. Sugiyama, K. Takagi, N. Takagi, S. Takeo, O. Tanaka, I. Yamato, K. Torigoe and R.S. Nowakowski (2003) Rapid appearance of pathological changes of neurons and glia cells in the cerebellum of microsphere-embolized rats. Brain Res. 978(1-2): 228-32. Caviness, V.S., Jr., T. Goto, T. Tarui, T. Takahashi, P. G. Bhide and R.S. Nowakowski (2002) Cell Output, Cell Cycle Duration and Neuronal Specification: A Model of Integrated Mechanisms of the Neocortical Proliferative Process. Cerebral Cortex 13:592–598. Cai, L., N.L. Hayes, T. Takahashi, V.S. Caviness, Jr., and R.S. Nowakowski (2002) Size distribution of retrovirally marked lineages matches prediction from population measurements of cell cycle behavior in early developing mouse neocortex. J. Neurosci. Res. 69:731-744. Rachel, R.A., G. Dölen, N.L. Hayes, A. Lu, L. Erskine, R.S. Nowakowski, and C.A. Mason (2002) Spatiotemporal alterations in neurogenesis in the albino retina. J. Neurosci. 22:4249-4263. Hayes, N.L. and R.S. Nowakowski (2000) Exploiting the dynamics of S-phase tracers in developing brain: Interkinetic nuclear migration for cells entering vs leaving the S-phase. Dev. Neurosci. 22: 44-55. Caviness, V.S., Jr., Takahashi, T., and Nowakowski, R.S. (1999) The G1 restriction point as a critical regulator of neocortical neuronogenesis. Neurochem. Res. 24(4):497-506 |
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