bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Ноя. 20, 2023
Abstract
In
the
developing
liver,
bipotent
epithelial
progenitor
cells
known
as
hepatoblasts
undergo
lineage
segregation
to
form
two
major
cell
types,
hepatocytes
that
constitute
bulk
of
liver
parenchyma
and
biliary
(cholangiocytes)
which
comprise
bile
duct,
a
complex
tubular
network
is
critical
for
normal
function.
Notch
TGFβ
signalling
promote
formation
sheet
cells,
ductal
plate
organises
into
discontinuous
structures.
How
these
structures
elongate
connect
continuous
duct
remains
undefined.
Here,
we
show
planar
polarity
protein,
VANGL2
expressed
late
in
intrahepatic
development
patterns
cell-cell
contacts
between
cells.
The
patterning
regulates
polarisation
actin
cytoskeleton
within
loss
Vangl2
-function
results
abnormal
distribution
cortical
remodelling
resulting
failure
formation.
Planar
step
post-specification
sculpture
essential
establishing
tissue
architecture.
Cells,
Год журнала:
2023,
Номер
12(3), С. 447 - 447
Опубликована: Янв. 30, 2023
Colorectal
cancer
(CRC)
represents
one
of
the
most
common
cancers
worldwide,
with
a
high
mortality
rate
despite
decreasing
incidence
and
new
diagnostic
therapeutic
strategies.
CRC
arises
from
both
epidemiologic
molecular
backgrounds.
In
addition
to
hereditary
factor
genetic
mutations,
strongly
varying
is
closely
linked
chronic
inflammatory
disorders
intestine
terrible
dietary
habits.
The
Wnt
signalling
pathway
complex
regulatory
network
that
implicated
in
many
physiological
processes,
including
occurrence,
development,
prognosis,
invasion,
metastasis.
It
currently
believed
include
classical
Wnt/β-catenin,
Wnt/PCP,
Wnt/Ca2+.
this
review,
we
summarise
recent
mechanisms
potential
regulators
three
branches
CRC.
Science Signaling,
Год журнала:
2023,
Номер
16(794)
Опубликована: Июль 18, 2023
Helicobacter
pylori
strains
that
deliver
the
oncoprotein
CagA
into
gastric
epithelial
cells
are
major
etiologic
agents
of
upper
diseases
including
cancer.
promotes
carcinogenesis
through
interactions
with
multiple
host
proteins.
Here,
we
show
also
disrupts
Wnt-dependent
planar
cell
polarity
(Wnt/PCP),
which
orients
within
plane
an
epithelium
and
coordinates
collective
behaviors
such
as
convergent
extension
to
enable
elongation
during
development.
Ectopic
expression
in
Xenopus
laevis
embryos
impaired
gastrulation,
neural
tube
formation,
axis
elongation,
processes
driven
by
movements
depend
on
Wnt/PCP
pathway.
Mice
specifically
expressing
stomach
had
longer
pyloric
glands
mislocalization
tetraspanin
proteins
VANGL1
VANGL2
(VANGL1/2),
critical
components
signaling.
The
increased
gland
length
was
due
hyperproliferation
at
base,
where
Lgr5
+
stem
progenitor
reside,
associated
fewer
differentiated
enteroendocrine
cells.
In
cultured
human
cells,
N
terminus
interacted
C-terminal
cytoplasmic
tails
VANGL1/2,
signaling
inducing
VANGL1/2
from
plasma
membrane
cytoplasm.
Thus,
may
contribute
development
cancer
subverting
a
Wnt/PCP-dependent
mechanism
restrains
proliferation
differentiation.
Molecular and Cellular Biochemistry,
Год журнала:
2023,
Номер
479(5), С. 1199 - 1221
Опубликована: Июнь 26, 2023
Abstract
Prickle
is
an
evolutionarily
conserved
family
of
proteins
exclusively
associated
with
planar
cell
polarity
(PCP)
signalling.
This
signalling
pathway
provides
directional
and
positional
cues
to
eukaryotic
cells
along
the
plane
epithelial
sheet,
orthogonal
both
apicobasal
left–right
axes.
Through
studies
in
fruit
fly
Drosophila
,
we
have
learned
that
PCP
manifested
by
spatial
segregation
two
protein
complexes,
namely
Prickle/Vangl
Frizzled/Dishevelled.
While
Vangl,
Frizzled,
Dishevelled
been
extensively
studied,
has
largely
neglected.
likely
because
its
role
vertebrate
development
pathologies
still
being
explored
not
yet
fully
understood.
The
current
review
aims
address
this
gap
summarizing
our
knowledge
on
cover
their
broad
versatility.
Accumulating
evidence
suggests
involved
many
developmental
events,
contributes
homeostasis,
can
cause
diseases
when
expression
properties
are
deregulated.
highlights
importance
development,
discusses
implications
Prickle-dependent
pathology,
points
out
blind
spots
or
potential
links
regarding
Prickle,
which
could
be
studied
further.
In
neurons,
the
acquisition
of
a
polarized
morphology
is
achieved
upon
outgrowth
single
axon
from
one
several
neurites.
Small
extracellular
vesicles
(sEVs),
such
as
exosomes,
diverse
sources
are
known
to
promote
neurite
and
thus
may
have
therapeutic
potential.
However,
effect
fibroblast-derived
exosomes
on
elongation
in
neurons
central
nervous
system
under
growth-permissive
conditions
remains
unclear.
Here,
we
show
that
sEVs
neuronal
mouse
primary
embryonic
cortical
neurons.
Mechanistically,
demonstrate
sEV-induced
increase
requires
endogenous
Wnts
core
PCP
components
including
Prickle,
Vangl,
Frizzled,
Dishevelled.
We
internalized
by
colocalize
with
Wnt7b,
induce
relocalization
Vangl2
distal
during
outgrowth.
contrast,
derived
or
astrocytes
do
not
outgrowth,
while
activated
inhibit
elongation.
Thus,
our
data
reveal
through
Wnt-PCP
pathway
manner
dependent
Wnts.
Vangl2,
a
core
component
of
the
PCP
signaling
pathway,
serves
as
scaffold
protein
on
cell
membrane,
playing
crucial
role
in
organizing
complexes.
Cilia,
dynamic
structures
surface,
carry
out
wide
range
functions.
Research
has
highlighted
bidirectional
regulatory
interaction
between
Vangl2
and
cilia,
underscoring
their
interconnected
roles
cellular
processes.
This
relationship
is
demonstrated
by
localization
at
base
proximal
regions
where
it
plays
essential
ciliary
positioning,
asymmetric
distribution,
ciliogenesis.
In
contrast,
absence
cilia
can
disrupt
Vangl2-mediated
signal
transduction
review
offers
narrative
recent
research
Vangl2's
function
examines
effects
signaling.
Developmental Biology,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 1, 2025
Many
mammalian
organs,
such
as
the
mammary
and
lachrymal
glands,
kidney
lungs
develop
by
process
known
branching
morphogenesis.
An
essential
feature
of
this
is
reciprocal
interaction
between
inner
branched
tubular
epithelium
surrounding
mesenchyme
to
optimize
final
amount
epithelial
tissue
that
generated
for
specific
functions.
To
achieve
expansion
initial
population
undergoes
repeated
rounds
bud
formation,
branch
outgrowth
tip
bifurcations,
with
each
repertoire
requiring
dynamic
changes
in
cell
behavior.
The
morphogenesis
was
first
studied
experimentally
Grobstein
others
who
showed
embryonic
did
not
without
so-called
inductive
signals
from
mesenchyme.
However,
it
whether
activity
uniformly
distributed
throughout
mesoderm
or
localized
regions.
mouse
lung
seen
a
powerful
system
which
investigate
questions
since
its
early
highly
stereotypic,
both
vivo
culture.
This
advantage
exploited
two
young
scientists,
Alescio
Cassini,
used
grafting
techniques
explanted
lungs.
They
around
distal
buds
could
induce
ectopic
trachea
other
non-branching
regions
epithelium.
At
same
time,
denuded
their
failed
further.
speculated
factors
promote
formation
continued
competent
endoderm
are
specifically
within
mesenchyme,
establishing
conceptual
framework
future
experimentation.
Since
then,
advances
many
areas
biology
bioengineering
have
enabled
identification
gene
regulatory
networks,
signaling
pathways
biomechanical
properties
mediate
quantitative
model
how
these
parameters
coordinated
over
space
time
control
pattern
scale
overall
size
lung,
still
remains
elusive.
Frontiers in Cell and Developmental Biology,
Год журнала:
2025,
Номер
13
Опубликована: Май 1, 2025
Frizzled
(FZD)
receptors
are
a
subset
of
G-protein-coupled
(GPCRs),
the
largest
class
human
cell
surface
and
major
target
FDA-approved
drugs.
Activated
by
Wnt
ligands,
FZDs
regulate
key
cellular
processes
such
as
proliferation,
differentiation,
polarity,
positioning
them
at
intersection
developmental
biology
disease,
including
cancer.
Despite
their
significance,
FZD
signaling
remains
incompletely
understood,
particularly
in
distinguishing
receptor-specific
roles
across
canonical
non-canonical
pathways.
Challenges
include
defining
ligand-receptor
specificity,
elucidating
signal
transduction
mechanisms,
understanding
influence
post
translational
modifications
context.
Structural
dynamics,
receptor
trafficking,
contributions
also
remain
areas
active
investigation.
Recent
advances
structural
biology,
transcriptomics,
functional
genomics
beginning
to
address
these
gaps,
while
emerging
therapeutic
approaches-such
small-molecule
modulators
antibodies-highlight
potential
drug
targets.
This
review
synthesizes
current
insights
into
examines
ongoing
controversies,
outlines
promising
directions
for
future
research
development.
Journal of Hepatology,
Год журнала:
2024,
Номер
81(1), С. 108 - 119
Опубликована: Март 7, 2024
In
the
developing
liver,
bipotent
epithelial
progenitor
cells
undergo
lineage
segregation
to
form
hepatocytes,
which
constitute
bulk
of
liver
parenchyma,
and
biliary
(cholangiocytes),
comprise
bile
duct
(a
complex
tubular
network
that
is
critical
for
normal
function).
Notch
TGFβ
signalling
promote
formation
a
sheet
cells,
ductal
plate,
organises
into
discontinuous
structures.
How
these
structures
elongate
connect
continuous
remains
undefined.
We
aimed
define
mechanisms
by
plate
transitions
from
simple
connected
duct.