The role of RhoA in corticogenesis

Insights into the developmental processes during which the brain
forms from the neuroepithelium may provide a deeper understanding
how the brain works. The Rho family of small GTPases is known for
its many cell biological functions such as regulation of the
cytoskeleton, gene expression, cell migration, adhesion, cell
polarity and the cell cycle. All of these functions are of
importance during the formation of the cerebral neocortex, which
consists of the generation of its different cell types, their
migration to their destination and their maturation to a functional
network. These roles have been mostly established in vitro using
dominant negative or constitutively active constructs. Since these
approaches are often not entirely specific for single pathways,
this work used the Cre/loxP system to genetically delete an
individual member of the Rho family, RhoA, to examine its role
following a loss-of-function approach. Specifically, we examined a
mouse line where part of the RhoA gene has been deleted by means of
the Emx1::Cre mouse line. This idea is based on previous
experiences with the deletion of Cdc42 in the developing neocortex,
which leads to a loss of apical progenitors. RhoA often works as a
functional antagonist to Cdc42. Using immunofluorescence, we could
detect a loss of RhoA at embryonic day 12 (E12) in
Emx1::Cre-positive offspring carrying the floxed RhoA-construct in
both alleles (cKO). At E14, we detected an increase in mitotic
cells to 160% (±25%, p