Actin Isoforms in Neuronal Development and Function - International Review of Cell and Molecular Biology - page 191

mice, as in humans, adult neurogenesis is confined to the subventricular
zone and the dentate gyrus of the hippocampus ( Lledo et al., 2006 ). New
neurons generated within the subventricular zone migrate along a defined
path composing the rostral migratory stream to the olfactory bulb where
they integrate into existing circuits ( Alvarez-Buylla and Garcia-Verdugo,
2002 ). The functional role that these neurons play has been somewhat con-
troversial, although some studies have demonstrated that these new neurons
facilitate odor discrimination and olfactory memory ( Enwere et al., 2004 ;
Gheusi et al., 2000 ). Interestingly, adult neurogenesis in the subventricular
zone increases significantly during late pregnancy in mice ( Shingo et al.,
2003 ), raising the possibility that these new neurons could play a role in
pup recognition, a critical factor leading to the proper retrieval and onset of
maternal behaviors. In the dentate gyrus of the hippocampus, the function
of adult neurogenesis is similarly controversial, but has been shown to cor-
relate positively with hippocampal-dependent learning paradigms ( Clelland
et al., 2009 ; Deng et al., 2010 ; Shors et al., 2001 ).
Given that the loss of β-actin has recently been demonstrated to severely
impair cell growth and division, and that newly generated neurons in adults
must migrate sometimes significant distances to integrate properly into syn-
aptic circuits, it is enticing to speculate that adult neurogenesis may also be
perturbed in CNS- Actb KO mice. Early experiments have not provided con-
clusive evidence yet, however. Despite a peculiar response to water, CNS-
Actb KO mice exhibited normal olfactory discrimination, a behavior linked
to adult neurogenesis ( Fig. 4.6 ). However, the abnormal behavior exhibited
by CNS- Actb KO mice in the Morris water maze could potentially be due
to disrupted adult neurogenesis in the dentate gyrus. More definitive experi-
ments remain to be conducted, including BrdU labeling in adult animals
to directly assess the number and localization of newly generated neurons
in CNS- Actb KO brains. Another particularly useful tool would be to cross
the conditional β-actin allele to an inducible Nestin-Cre ER transgenic line,
which is expressed only after induction in neural progenitors in adult animals
( Chen et al., 2009 ). Such an experiment would provide additional direct evi-
dence for a role of β-actin in adult neurogenesis and associated behaviors.
6.2. Insight from ZBP1 Knockout and Heterozygous Mouse
Studies
If ZBP1 is critical for the localization and function of β-actin in neurons
in vivo, one might expect that a ZBP1 KO mouse would phenocopy or
exhibit even a more severe phenotype than CNS- Actb KO mice due to the