Genetic control of hippocampal neurogenesis

Neurogenesis - the production of new neurons - is an ongoing process that persists in the adult brain of several species, including humans. It has been most intensively studied in the mouse in two discrete brain regions: the subventricular zone (SVZ) lining the lateral wall of the lateral ventricles; and the subgranular zone (SGZ) of the dentate gyrus of the hippocampus [1] (Figure 1). These regions harbor relatively quiescent astrocyte-like stem cells, which divide and give rise to multipotential, rapidly dividing transit-amplifying cells that will eventually differentiate into neuroblasts. These later generate neuroblasts that are believed to have limited further mitotic potential [2,3]. Neuroblasts from the SVZ and SGZ migrate and eventually mature into functional neurons within the olfactory bulb and dentate gyrus, respectively. Most recent evidence suggests that the stem cells in these regions can also give rise to astrocytes and oligodendrocytes of the glial lineage, indicating that in vivo, as in vitro, these cells are multipotent [4]. A recent study by Kempermann et al. [5] in the Proceedings of the National Academy of Sciences of the USA sheds interesting new light on the genetic complexity of the regulation of neurogenesis.Several groups have found significant differences in proliferation and neuronal survival in the dentate gyrus between several common mouse strains, suggesting a strong degree of genetic regulation of this process. In an earlier study, Kempermann and colleagues [6] used stereology, the quantitative analysis of neurological parameters, in combination with sequential labeling of S-phase cells by bromodeoxyuridine (BrdU) injections to show that genetic variation among strains accounted for differences in all aspects of hippocampal neurogenesis, proliferation, survival and differentiation, as well as overall hippocampal volume and total cell numbers. Proliferation was found to be the highest in the C57BL/6 strain, for instance, whereas CD1 mi