Biomedical Engineering Reference
In-Depth Information
and narrowing of the neural plate, as measured by the increase of the length-
to-width ratio. Significantly, the reduction of length-to-width ratio in
Dvl1
/
;
Dvl2
/
and
Lp/Lp
mutants is observed from 4-somite
stage, the earliest time point when length-to-width ratio can be
determined and several hours before neural tube closure occurs in control
embryos (
Wang, Hamblet, et al., 2006
). Thus, a Dvl/Vangl-mediated
homologous PCP pathway is important for a convergent extension-like
morphogenetic process during neurulation to reduce the width of the
neural plate, which may facilitate neural tube closure by shortening the
distance between the opposing neural folds (
Wallingford & Harland,
2002
). Consistent with this idea,
Dvl2
/
;
Lp/
þ
mutants also show
significantly reduced length-to-width ratio as
Dvl1
/
;
Dvl2
/
and
Lp/
Lp
and fail to closure their neural tubes, while
Lp/
þ
mutants display
moderate reduction of the length-to-width ratio and delayed neural tube
closure (
Wang, Hamblet, et al., 2006
).
3.3. PCP pathway in axonal tract development
In addition to its documented roles during neurulation and inner ear devel-
opment, accumulating evidence has linked the noncanonical Wnt pathway to
axonal tract development. Mutation of
Celsr3
,another
flamingo/starry night
mouse homolog, leads to the absence of the internal capsule, anterior
commissure, and many of the longitudinal axonal bundles, disconnecting
the cortex from subcortical structures (
Tissir, Bar, Jossin, De Backer, &
Goffinet, 2005
).
Fz3
null mutants (
Wang, Thekdi, Smallwood, Macke, &
Nathans, 2002
) or embryos with knock-down of
Dvls
(
Zhang et al., 2007
)
display almost identical abnormalities, strongly implying that the noncanonical
Wnt pathway/PCP is involved in axon tract development in the central
nervous system.
3.4. PCP pathway during gastrulation: mouse prickle-1 (mpk1)
is essential for epiblast AB polarity
The canonical Wnt pathway is not the only Wnt-related pathway important
for gastrulation. Recently, Tao et al. (2009) found that the deletion of
mpk1
gene resulted in early embryonic lethality, between E5.5 and E6.5, associ-
ated with failure of DVE migration and primitive streak formation. Mutant
epiblast tissue was disorganized, and epiblast cells displayed abnormal cell
shapes, mislocalized ECM proteins, and disrupted orientation of mitotic
spindles with loss of AB polarity of epiblast cells. They demonstrated that
