Richard S. Nowakowski Professor UMDNJ- RWJ Medical School Dept. of Neuroscience & Cell Biology 675 Hoes Lane Piscataway. NJ 08854 (732) 235-4981 FAX - 4029 rsn@umdnj.edu Visit Dr. Nowakowski's Homepage!

Cell proliferation. cell cycle and proliferative fates of sister cells during the development of the vertebrate cerebral cortex and during adult neurogenesis

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. bromodeoxyuridine 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 have correlated changes in the direction and rate movements of cell nuclei with phases of the cell cycle. In addition. we have documented systematic increases in the length of the cell cycle during development and in the proportion of daughter cells that re-enter the proliferative populations (the P-fraction) as opposed to these that leave the proliferative populations (the Q-fraction). Thus. the average behavior of the proliferative populations is consistent with independence of proliferative fates for daughter cells resulting from single mitotic event. The regulation of this proliferative behavior by competition for endogenous growth factors is the current major direction of research in this laboratory. Mathematical models and computer simulations are used to provide a framework for hypothesis development and testing.

Selected Publications

Nowakowski RS, Hayes NL. (2008) Radiation, retardation and the developing brain: time is the crucial variable. Acta Paediatr. 97(5):527-31.

Suter B, Nowakowski RS, Bhide PG, Caviness VS. (2007) Navigating neocortical neurogenesis and neuronal specification: a positional information system encoded by neurogenetic gradients. J Neurosci. 27(40):10777-84.

Nowakowski RS. (2006) Stable neuron numbers from cradle to grave. Proc Natl Acad Sci U S A. 103(33):12219-20.

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.

Zheng W, Nowakowski RS, Vaccarino FM. (2004) Fibroblast growth factor 2 is required for maintaining the neural stem cell pool in the mouse brain subventricular zone. Dev Neurosci. 26(2-4):181-96.

Sekiguchi M. Sugiyama Y. Takagi K. Takagi N. Takeo S. Tanaka O. Yamato I. Torigoe K. Nowakowski RS. (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 VS Jr. Goto T. Tarui T. Takahashi T. Bhide PG. Nowakowski RS. (2003) Cell output. cell cycle duration and neuronal specification: a model of integrated mechanisms of the neocortical proliferative process. Cereb Cortex. 13(6):592-8.

Nowakowski RS. Caviness VS Jr. Takahashi T. Hayes NL. (2002) Population dynamics during cell proliferation and neuronogenesis in the developing murine neocortex. Results Probl Cell Differ. 39:1-25. Review.

Cai L. Hayes NL. Takahashi T. Caviness VS Jr. Nowakowski RS. (2002) Size distribution of retrovirally marked lineages matches prediction from population measurements of cell cycle behavior. J Neurosci Res. 69(6):731-44.

Goto T. Takahashi T. Miyama S. Nowakowski RS. Bhide PG. Caviness VS Jr. (2002) Developmental regulation of the effects of fibroblast growth factor-2 and 1-octanol on neuronogenesis: implications for a hypothesis relating to mitogen-antimitogen opposition. J Neurosci Res. 69(6):714-22.

Rachel RA. Dolen G. Hayes NL. Lu A. Erskine L. Nowakowski RS. Mason CA. (2002)Spatiotemporal features of early neuronogenesis differ in wild-type and albino mouse retina. J Neurosci. 22(11):4249-63.

Hayes NL. Nowakowski RS. (2002) Dynamics of cell proliferation in the adult dentate gyrus of two inbred strains of mice. Brain Res Dev Brain Res. 134(1-2):77-85.

Nowakowski RS. Hayes NL. (2001) Stem cells: the promises and pitfalls. Neuropsychopharmacology. 25(6):799-804. Review.

Cahana A. Escamez T. Nowakowski RS. Hayes NL. Giacobini M. von Holst A. Shmueli O. Sapir T. McConnell SK. Wurst W. Martinez S. Reiner O. (2001) Targeted mutagenesis of Lis1 disrupts cortical development and LIS1 homodimerization. Proc Natl Acad Sci U S A. 98(11):6429-34.