Biomedical Engineering Reference
In-Depth Information
their axons toward their target tissue branchial arches. This collective migra-
tion is PCP dependent such that migration of FBM neurons is totally
abolished in the core PCP zebrafish mutants including
vangl2
,
scrb
,
fzd3a
,
and
celsr2
(if abrogated with Celsr1a/1b activities) (
Jessen et al., 2002; Wada
et al., 2006; Wada et al., 2005
) and morphants such as
pk1a
and
pk1b
(
Carreira-Barbosa et al., 2003; Mapp et al., 2010
). Importantly, it appears
that this process is Dsh-independent (
Bingham et al., 2002
). Different to
zebrafish, FBM neurons migrate in a sequential manner in mice in that the
neurons migrate caudally then laterally. This is evident in
celsr2;celsr3
double
mutants or
fzd3
mutants, in which caudal migration of FMB neurons is
suppressed while their lateral migration is relatively normal (
Qu et al., 2010
).
Both cell-autonomous (in migrating neurons) and cell-non-autonomous
(in the neuroepithelia) functions of PCP are required for proper collective
migration (
Jessen et al., 2002; Wada et al., 2005; Wada et al., 2006
).
Interestingly, Pk1b, whose expression is only in migrating neurons but not
in the neuroepithelia, mediates collective migration independently of PCP
function, and rather its ability is associated with its nuclear localization
(
Mapp et al., 2011
). In addition to Pk1b, forward genetic approach in
zebrafish identified a potential new mediator of PCP in this process. The
gene, which encodes Nance-Horan syndrome-like protein 1b with a
WAVE homology domain as a potential regulator of actin cytoskeleton, is
required only within the migrating neurons (
Walsh et al., 2011
). Currently,
it is unknown whether the PCP pathway controls cell cohesion of migrating
FBM neurons. Considering the fact that neurons possess higher cohesive
properties than surrounding neuroepithelial cells (
Stockinger et al., 2011
), it
would be plausible since Pk is required for cohesive properties of migrating
dorsal forerunner cells during zebrafish gastrulation (
Oteiza et al., 2010
).
The interpretation for cell-nonautonomous requirement of the PCP
pathway in the zebrafish neuroepithelia is a complex issue as to what a pri-
mary defect is. In contrast to other vertebrates, zebrafish neurulation
involves oriented cell division (crossing-division) that creates the neural tube
with a lumen from the neural keel mediated by polarized mesenchymal cells
(
Tawk et al., 2007
). Despite the ability of the cells to stretch and to acquire
apicobasal polarity along the mediolateral axis of the embryo, the core PCP
mutants exhibit defects in several different aspects of morphogenesis during
neurulation such as the orientation and planar polarization of the cells in
their AP axis and ectopic lumen formation (
Ciruna et al., 2006; Tawk
et al., 2007; Zigman et al., 2011
). In addition, proper coherent properties
of neuroepithelia allow a coherent cluster of FBM neurons to migrate
