Mechanical
forces
are
well
known
for
modulating
heart
valve
developmental
programs.
Yet,
it
is
still
unclear
how
genetic
programs
and
mechanosensation
interact
during
development.
Here,
we
assessed
the
mechanosensitive
pathways
involved
zebrafish
outflow
tract
(OFT)
development
in
vivo.
Our
results
show
that
hippo
effector
Yap1,
Klf2,
Notch
signaling
pathway
all
essential
OFT
morphogenesis
response
to
mechanical
forces,
albeit
active
different
cell
layers.
Furthermore,
Piezo
TRP
channels
important
factors
these
pathways.
In
addition,
live
reporters
reveal
controls
Klf2
activity
endothelium
Yap1
localization
smooth
muscle
progenitors
coordinate
morphogenesis.
Together,
this
work
identifies
a
unique
morphogenetic
program
formation
places
as
central
modulator
of
process.
Science,
Journal Year:
2018,
Volume and Issue:
362(6413), P. 464 - 467
Published: Oct. 26, 2018
Activation
of
stretch-sensitive
baroreceptor
neurons
exerts
acute
control
over
heart
rate
and
blood
pressure.
Although
this
homeostatic
baroreflex
has
been
described
for
more
than
80
years,
the
molecular
identity
mechanosensitivity
remains
unknown.
We
discovered
that
mechanically
activated
ion
channels
PIEZO1
PIEZO2
are
together
required
baroreception.
Genetic
ablation
both
Piezo1
Piezo2
in
nodose
petrosal
sensory
ganglia
mice
abolished
drug-induced
aortic
depressor
nerve
activity.
Awake,
behaving
animals
lack
Piezos
had
labile
hypertension
increased
pressure
variability,
consistent
with
phenotypes
baroreceptor-denervated
humans
failure.
Optogenetic
activation
Piezo2-positive
afferents
was
sufficient
to
initiate
mice.
These
findings
suggest
long-sought
mechanosensors
critical
control.
Mechanically
activated
(MA)
ion
channels
convert
physical
forces
into
electrical
signals,
and
are
essential
for
eukaryotic
physiology.
Despite
their
importance,
few
bona-fide
MA
have
been
described
in
plants
animals.
Here,
we
show
that
various
members
of
the
OSCA
TMEM63
family
proteins
from
plants,
flies,
mammals
confer
mechanosensitivity
to
naïve
cells.
We
conclusively
demonstrate
OSCA1.2,
one
Arabidopsis
thaliana
proteins,
is
an
inherently
mechanosensitive,
pore-forming
channel.
Our
results
suggest
OSCA/TMEM63
largest
identified,
conserved
across
eukaryotes.
findings
will
enable
studies
gain
deep
insight
molecular
mechanisms
channel
gating,
facilitate
a
better
understanding
mechanosensory
processes
vivo
Mechanical
load
of
the
skeleton
system
is
essential
for
development,
growth,
and
maintenance
bone.
However,
molecular
mechanism
by
which
mechanical
stimuli
are
converted
into
osteogenesis
bone
formation
remains
unclear.
Here
we
report
that
Piezo1,
a
bona
fide
mechanotransducer
critical
various
biological
processes,
plays
role
in
formation.
Knockout
Piezo1
osteoblast
lineage
cells
disrupts
osteoblasts
severely
impairs
structure
strength.
Bone
loss
induced
unloading
blunted
knockout
mice.
Intriguingly,
simulated
microgravity
treatment
reduced
function
suppressing
expression
Piezo1.
Furthermore,
osteoporosis
patients
show
closely
correlated
with
dysfunction.
These
data
collectively
suggest
functions
as
key
conferring
mechanosensitivity
to
determining
mechanical-load-dependent
formation,
represents
novel
therapeutic
target
treating
or
unloading-induced
severe
loss.
Mechanical
loading,
such
as
caused
by
exercise,
stimulates
bone
formation
osteoblasts
and
increases
strength,
but
the
mechanisms
are
poorly
understood.
Osteocytes
reside
in
matrix,
sense
changes
mechanical
load,
produce
signals
that
alter
osteoblasts.
We
report
ion
channel
Piezo1
is
required
for
gene
expression
induced
fluid
shear
stress
cultured
osteocytes
stimulation
of
a
small
molecule
agonist
sufficient
to
replicate
effects
flow
on
osteocytes.
Conditional
deletion
notably
reduced
mass
strength
mice.
Conversely,
administration
adult
mice
increased
mass,
mimicking
loading.
These
results
demonstrate
mechanosensitive
which
osteoblast
lineage
cells
respond
load
identify
novel
target
anabolic
therapy.
