Actin Isoforms in Neuronal Development and Function - International Review of Cell and Molecular Biology - page 186

cerebellum, for example, we found variable abnormal organization or
branching of the cerebellar folia ( Fig. 4.4 , asterisks). Within the hippocam-
pus, significant displacement of the dentate gyrus and hippocampal fissure
was observed resulting in decreased CA1 cell density localized to the den-
tate gyrus/hippocampal fissure invagination ( Fig. 4.4 red arrows and aster-
isks). Intriguingly, the cerebellum and hippocampus undergo somewhat
similar developmental programs during morphogenesis, which may shed
light on the mechanisms underlying the specific abnormalities observed.
The developing cerebellum, for example, starts off as a relatively smooth,
elongated sphere in the mouse hindbrain. Later, a select population of cells
is thought to attach to the extracellular matrix (ECM) or another cell type,
thereby forming hingepoints through which the developing cerebellar folia
grow out from (Sudarov and Joyner, 2007) . The abnormal positioning and
organization of the cerebellar folia in CNS- Actb KO mice suggests that
β-actin may perform a specific function in the regulation of hingepoint
specification and positioning, potentially by mediating cell-ECM or cell-cell
adhesions.
The morphological abnormalities observed in the hippocampus may
also share a common mechanism with those described in the cerebel-
lum. The developing hippocampus begins essentially as a thin sheet of
cells where select anchor points are established causing the hippocampus
to fold in on itself as it enlarges, creating the hippocampal fissure and its
recognizable interlocking “C” morphology ( Eckenhoff and Rakic, 1984 ;
Smart, 1982 ). Histological data from CNS- Actb KO mice suggest that the
folding of the hippocampus occurs abnormally in the absence of β-actin,
leading to the displacement of the hippocampal fissure, dentate gyrus, and
adjacent CA1 region ( Fig. 4.4 ) likely via impaired regulation of cell-ECM
or cell-adhesions.
There may also be an even more direct connection between a specific
role for β-actin and the cellular constriction that promotes tissue bending
during brain morphogenesis. Tissue bending similar to what occurs during
the development of the cerebellum and hippocampus is perhaps best mod-
eled by neural tube closure, where cells at the hingepoints of the neural
tube undergo an actin and myosin-mediated apical constriction causing
adjacent cells to be pulled inward and bending the tissue ( Copp et al., 2003 ;
Martin, 2010 ). Interestingly, β-actin has been found to be specifically
enriched at the cleavage furrow of dividing cells in culture, suggesting
that β-actin within the actin-myosin contractile rings may be particularly
important for cellular constriction during cell division and tissue bending