UMDNJ
Robert Wood Johnson Medical School
675 Hoes Lane
Piscataway, NJ 08854

lab: (732) 235-4647
office: (732) 235-4527

FAX: (732) 235-4029

hayes@umdnj.edu

Genetic regulation of cell proliferation and neurogenesis in the mouse CNS.

• Mouse mutants
• Cell cycle analyis

Proliferating cells that produce both neurons and glia have been demonstrated in the adult dentate gyrus (DG) of many mammals including mice, rats, monkeys, and humans. The identity of some or all of these proliferating cells as “stem” cells is of significance to numerous disciplines in both basic and clinical science. One goal of our work is to define quantitatively the proliferating population in the DG of adult mice and the dynamics of their proliferation and survival. This information will clarify and advance understanding of the characteristics of stem vs progenitor cells within the adult. A second goal is to begin to identify the genetic controls of adult proliferation by building upon an important set of experiments in which we found that genetic regulation of the size of the proliferating population (stem or progenitor) in the DG is independent of the genetic regulation of cell death (or the survival potential) among the newly produced cells. These results showd that 1) in two inbred strains of mice (C57BL/6J and BALB/cByJ), the size of the proliferating population differs maximally while the proportion of newly produced cells which survive for =6 weeks is similar (~S-phase cohort ± 10%)., and 2) DBA/2J and C3H/HeJ have an S-phase population similar in size to BALB/cByJ, but the surviving cells after 6 weeks comprise <50% of the S-phase cohort in DBA/2 and >80% in C3H/He. Specifically we are examining: 1) the role of cell cycle kinetics in strain differences, 2) the dynamics and proportional contributions of proliferation and survival to maintaining the size of the intrahilar proliferative population, and 3) the extent of cell death in the proliferating and post-proliferative populations, all in a wide sampling of inbred and recombinant inbred strains of mice. These findings of these experiments are of direct relevance to our understanding of both the role and potential of neuronal stem cells in the function and repair of the brain and spinal cord and mark the first steps toward elucidating the genes that are involved.

For complete list: PubMed

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

Cahana, A., T. Escamez, R.S. Nowakowski, N.L. Hayes, M.B. Giacobini, A. von Holst, O. Shmueli, T. Sapir, S. K. McConnell, W. Wurst, S. Martinez, and O. Reiner (2001) Targeted mutagenesis of Lis1 disrupts cortical development and LIS1 homodimerization. PNAS 98: 6429-6434.

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.