bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2022,
Номер
unknown
Опубликована: Май 4, 2022
Abstract
Background
Limb
buds
develop
as
bilateral
outgrowths
of
the
lateral
plate
mesoderm
and
are
patterned
along
three
axes.
Current
models
proximal
to
distal
patterning
early
amniote
limb
suggest
that
two
signals,
a
organising
signal
from
apical
epithelial
ridge
(AER,
Fgfs)
an
opposing
(retinoic
acid)
act
on
pattern
this
axis.
Results
Transcriptional
analysis
stage
51
Xenopus
laevis
hindlimb
sectioned
proximal-distal
axis,
showed
region
is
distinct
rest
limb.
Expression
capn8
.
3
,
novel
calpain,
was
located
in
cells
immediately
flanking
AER.
The
Wnt
antagonist
Dkk1
AER-specific
limbs.
Two
transcription
factors,
sall1
zic5
were
expressed
mesenchyme.
Zic
5
has
no
described
association
with
development.
We
also
describe
expression
genes,
gata5
tnn
not
previously
associated
Differentially
genes
Fgf,
retinoic
acid
(RA)
signalling
well
differential
cell
adhesion
proliferation.
Conclusions
identify
new
candidate
for
proximodistal
patterning.
Our
RA-regulated
supports
role
transient
RA
gradients
bud
proximal-to-distal
anamniote
model
organism.
The
mechanobiology
of
cartilage
during
limb
growth
represents
a
complex
interplay
between
mechanical
forces
and
biological
processes.
However,
the
fundamental
processes
that
involve
formation
from
mesenchymal
stem
cells
are
not
fully
understood.
Further,
cellular
level
response
in
its
native
environment
under
physiological
load
is
characterized.
This
thesis
aims
to
bridge
critical
gaps
our
understanding
development
regeneration
by
investigating
nuanced
interactions
mechanics
within
cartilaginous
tissues.
Identifying
these
research
gaps,
this
encompasses
three
specific
aims.
Aim
1
focuses
on
characterizing
viscoelastic
material
properties
growing
limbs,
employing
axolotls
as
an
animal
model.
Our
results
reveal
significant
increases
both
instantaneous
equilibrium
shear
moduli
regeneration,
coupled
with
notable
changes
short-
long-term
stress
relaxation
times.
glycosaminoglycan
content
also
development.
2
explores
calcium
signaling
in-situ
chondrocytes
physiologically
relevant
cyclic
loads
dynamic
hydrostatic
pressure.
findings
underscore
strain
rate-dependent
increase
percentage
responsive
compressive
loads,
non-distinct
time
characteristics
across
loading
conditions.
Conversely,
low
magnitude
pressure
showed
no
impact
chondrocytes.
3
investigates
expression
mechanosensitive
ion
channels
(TRPV4,
PIEZO1,
PIEZO2)
axolotl
regeneration.
study
unveils
presence
TRPV4
PIEZO2
blastemal
early
late
heightened
condensing
mesenchyme
These
taken
together
shed
light
intricate
responses.
implications
abnormal
mechanobiological
profound,
contributing
developmental
disorders
musculoskeletal
diseases.
Understanding
mechanisms
conditions
opens
avenues
for
therapeutic
strategies
aimed
at
promoting
proper
mitigating
skeletal
abnormalities.
Future
will
focus
elucidating
functional
roles
further
expanding
interconnections
biology.--Author's
abstract
Annals of the New York Academy of Sciences,
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 13, 2024
Abstract
Previous
studies
have
implicated
epithelial–mesenchymal
transition
(EMT)
in
salamander
limb
regeneration.
In
this
review,
we
describe
putative
roles
for
EMT
during
each
stage
of
regeneration
axolotls
and
other
salamanders.
We
hypothesize
that
EMT‐like
gene
expression
programs
may
regulate
three
main
cellular
processes
regeneration:
(1)
keratinocyte
migration
wound
closure;
(2)
transient
invasion
the
stump
by
epithelial
cells
undergoing
EMT;
(3)
use
non‐epithelial
blastemal
progenitor
to
escape
confines
their
niches.
Finally,
propose
nontraditional
warrant
further
investigation,
including
alternative
regulators,
stem
cell
activation,
fibrosis
induced
aberrant
EMT.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 20, 2024
Why
mammals
cannot
regenerate
limbs,
unlike
amphibians,
presents
a
longstanding
puzzle
in
biology.
We
show
that
exposing
ex
vivo
amputated
embryonic
mouse
limbs
to
subatmospheric
oxygen
environment,
or
stabilizing
oxygen-sensitive
HIF1A
enables
not
only
rapid
wound
healing,
but
alters
cellular
mechanics,
and
reshapes
the
histone
landscape
prime
regenerative
fates.
Conversely,
Xenopus
tadpole
display
low
oxygen-sensing
capacity,
robust
landscape,
glycolytic
programs
even
under
high
oxygen.
This
reduced
stark
contrast
mammals,
associates
with
decreased
HIF1A-regulating
gene
expressions.
Our
findings
thus
uncover
species-specific
sensing
as
unifying
mechanism
for
limb
regeneration
initiation
across
vertebrates,
reveal
how
aquatic
habitats
may
enhance
capabilities,
identify
targetable
barriers
unlock
latent
adult
mammals.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2022,
Номер
unknown
Опубликована: Май 4, 2022
Abstract
Background
Limb
buds
develop
as
bilateral
outgrowths
of
the
lateral
plate
mesoderm
and
are
patterned
along
three
axes.
Current
models
proximal
to
distal
patterning
early
amniote
limb
suggest
that
two
signals,
a
organising
signal
from
apical
epithelial
ridge
(AER,
Fgfs)
an
opposing
(retinoic
acid)
act
on
pattern
this
axis.
Results
Transcriptional
analysis
stage
51
Xenopus
laevis
hindlimb
sectioned
proximal-distal
axis,
showed
region
is
distinct
rest
limb.
Expression
capn8
.
3
,
novel
calpain,
was
located
in
cells
immediately
flanking
AER.
The
Wnt
antagonist
Dkk1
AER-specific
limbs.
Two
transcription
factors,
sall1
zic5
were
expressed
mesenchyme.
Zic
5
has
no
described
association
with
development.
We
also
describe
expression
genes,
gata5
tnn
not
previously
associated
Differentially
genes
Fgf,
retinoic
acid
(RA)
signalling
well
differential
cell
adhesion
proliferation.
Conclusions
identify
new
candidate
for
proximodistal
patterning.
Our
RA-regulated
supports
role
transient
RA
gradients
bud
proximal-to-distal
anamniote
model
organism.
