bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Июль 10, 2023
Abstract
The
ability
of
animals
to
regenerate
damaged
tissue
is
a
complex
process
that
involves
various
cellular
mechanisms.
As
age,
they
lose
their
regenerative
abilities,
making
it
essential
understand
the
underlying
mechanisms
limit
during
aging.
Drosophila
melanogaster
wing
imaginal
discs
are
epithelial
structures
can
after
injury.
While
significant
research
has
focused
on
investigating
responses
larval
stages,
particularly
regarding
regulation
and
function
JNK
pathway,
our
comprehension
potential
pupal
wings
contributing
decline
remains
limited.
This
study
explores
temporal
dynamics
development
proliferative
response
triggered
by
induction
cell
death,
typical
response.
Our
results
indicate
apoptosis-induced
proliferation
be
initiated
as
late
30
hours
pupa
formation
(APF),
when
in
normal
circumstances
ceases
at
around
20
APF.
Furthermore,
data
revealed
35
APF,
death
alone
fails
induce
further
proliferation.
Interestingly,
failure
reinitiating
cycle
beyond
this
time
point
not
attributed
an
incapacity
activate
pathway.
Instead,
one
constraining
factors
apoptotic-induced
seems
activity
level
ecdysone-responsive
genes.
Author
Summary
Animals
have
remarkable
tissues,
but
diminishes
with
age.
Understanding
age-related
abilities
crucial.
provide
valuable
model
for
studying
regeneration.
understanding
In
study,
we
investigate
development,
development.
findings
reveal
occur
even
ceased.
However,
stages
does
occur.
We
found
that,
inability
reinitiate
influenced
hormone
ecdysone
its-responsive
These
shed
light
dynamic
processes
involved
regeneration
expands
interplay
between
proliferation,
gene
regeneration,
providing
insights
future
biology.
Abstract
The
Drosophila
wing
imaginal
disc
is
a
tissue
of
undifferentiated
cells
that
are
precursors
the
and
most
notum
adult
fly.
first
forms
during
embryogenesis
from
cluster
∼30
located
in
second
thoracic
segment,
which
invaginate
to
form
sac-like
structure.
They
undergo
extensive
proliferation
larval
stages
mature
∼35,000
cells.
During
this
time,
distinct
cell
fates
assigned
different
regions,
develops
complex
morphology.
Finally,
pupal
undergoes
morphogenetic
processes
then
differentiates
notum.
While
bulk
comprises
epithelial
cells,
it
also
includes
neurons
glia,
associated
with
tracheal
muscle
precursor
relative
simplicity
accessibility
disc,
combined
wealth
genetic
tools
available
Drosophila,
have
make
premier
system
for
identifying
genes
deciphering
systems
play
crucial
roles
animal
development.
Studies
discs
made
key
contributions
many
areas
biology,
including
patterning,
signal
transduction,
growth
control,
regeneration,
planar
polarity,
morphogenesis,
mechanics.
Current Biology,
Год журнала:
2022,
Номер
32(15), С. 3350 - 3364.e6
Опубликована: Июль 11, 2022
An
important
unanswered
question
in
regenerative
biology
is
to
what
extent
regeneration
accomplished
by
the
reactivation
of
gene
regulatory
networks
used
during
development
versus
activation
regeneration-specific
transcriptional
programs.
Following
damage,
Drosophila
imaginal
discs,
larval
precursors
adult
structures,
can
regenerate
missing
portions
localized
proliferation
damage-adjacent
tissue.
Using
single-cell
transcriptomics
regenerating
wing
we
have
obtained
a
comprehensive
view
transcriptome
discs
and
identified
two
cell
populations
within
blastema,
Blastema1
Blastema2.
Collectively,
these
cells
upregulate
multiple
genes
encoding
secreted
proteins
that
promote
including
Pvf1,
upd3,
asperous,
Mmp1,
maturation
delaying
factor
Ilp8.
Expression
transcription
Ets21C
restricted
this
secretory
zone;
it
not
expressed
undamaged
discs.
expression
activated
JNK/AP-1
pathway,
function
type
1
coherent
feedforward
loop
with
AP-1
sustain
downstream
genes.
Without
function,
blastema
fail
maintain
number
genes,
which
leads
premature
differentiation
severely
compromised
regeneration.
As
dispensable
for
normal
development,
observations
indicate
orchestrates
network.
We
also
resembling
both
Blastema2
scribble
tumorous
They
express
Ets21C-dependent
network,
eliminating
reduces
growth.
Thus,
mechanisms
be
co-opted
tumors
aberrant
The Journal of Physiology,
Год журнала:
2024,
Номер
602(11), С. 2627 - 2648
Опубликована: Май 23, 2024
Homeostasis
constitutes
a
key
concept
in
physiology
and
refers
to
self-regulating
processes
that
maintain
internal
stability
when
adjusting
changing
external
conditions.
It
diminishes
entropy
constituting
driving
force
behind
evolution.
Natural
selection
might
act
on
homeostatic
regulatory
mechanisms
control
including
homeodynamics,
allostasis,
hormesis
homeorhesis,
where
different
stable
stationary
states
are
reached.
Regeneration
is
under
through
hormesis.
Damage
tissues
initiates
response
restore
the
impaired
equilibrium
caused
by
mild
stress
using
cell
proliferation,
differentiation
death
recover
structure
function.
Repair
homeorhetic
change
leading
new
state
with
decreased
functionality
fibrotic
scarring
without
reconstruction
of
3-D
pattern.
Mechanisms
determining
entrance
tissue
or
organ
regeneration
repair
include
balance
between
innate
adaptive
immune
cells
relation
plasticity
stromal
stem
responses,
redox
balance.
The
regenerative
reparative
capacities
vary
species,
distinct
organs,
at
stages
development
ageing.
Many
signals
pathways
play
crucial
roles
regulating
protein
synthesis,
cellular
growth,
inflammation,
autophagy,
lysosomal
function,
metabolism
metalloproteinase
signalling.
Attempts
favour
damaged
those
low
proliferative
rates
have
been
made;
however,
there
evolutionary
constraint
poor
proliferation
unfavourable
environments
tumour
development.
More
research
required
better
understand
these
mechanisms.
PLoS Genetics,
Год журнала:
2024,
Номер
20(9), С. e1011387 - e1011387
Опубликована: Сен. 3, 2024
A
programmed
developmental
switch
to
G
/
S
endocycles
results
in
tissue
growth
through
an
increase
cell
size.
Unscheduled,
induced
endocycling
cells
(iECs)
promote
wound
healing
but
also
contribute
cancer.
Much
remains
unknown,
however,
about
how
these
iECs
affect
growth.
Using
the
D
.
melanogaster
wing
disc
as
model,
we
find
that
populations
of
initially
size
then
subsequently
undergo
a
heterogenous
arrest
causes
severe
undergrowth.
acquired
DNA
damage
and
activated
Jun
N-terminal
kinase
(JNK)
pathway,
but,
unlike
other
stressed
cells,
were
apoptosis-resistant
not
eliminated
from
epithelium.
Instead,
entered
JNK-dependent
reversible
senescent-like
arrest.
Senescent
promoted
division
diploid
neighbors,
this
compensatory
proliferation
did
rescue
Our
study
has
uncovered
unique
attributes
their
effects
on
have
important
implications
for
understanding
roles
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Март 14, 2024
Summary
A
programmed
developmental
switch
to
G
/
S
endocycles
results
in
tissue
growth
through
an
increase
cell
size.
Unscheduled,
induced
endocycling
cells
(iECs)
promote
wound
healing
but
also
contribute
cancer.
Much
remains
unknown,
however,
about
how
these
iECs
affect
growth.
Using
the
D.
melanogaster
wing
disc
as
model,
we
find
that
populations
of
initially
size
then
subsequently
undergo
a
heterogenous
arrest
causes
severe
undergrowth.
acquired
DNA
damage
and
activated
Jun
N-terminal
kinase
(JNK)
pathway,
but,
unlike
other
stressed
cells,
were
apoptosis-resistant
not
eliminated
from
epithelium.
Instead,
entered
JNK-dependent
reversible
senescent-like
arrest.
Senescent
promoted
division
diploid
neighbors,
this
compensatory
proliferation
did
rescue
Our
study
has
uncovered
unique
attributes
their
effects
on
have
important
implications
for
understanding
roles
Insects,
Год журнала:
2025,
Номер
16(2), С. 124 - 124
Опубликована: Янв. 27, 2025
Insects
can
repair
wounds
and
regenerate
body
parts
in
response
to
physical
damage.
Wound
healing
butterfly
pupal
wing
tissues
is
developmentally
interesting
because
ectopic
color
patterns
develop
during
healing,
suggesting
that
normal
damage-induced
may
use
similar
mechanisms.
Here
we
physiologically
investigated
wound
pattern
formation
using
the
blue
pansy
Junonia
orithya.
In
puncture
damage,
various
are
formed
around
damage
site.
After
wounding
operation,
observed
hemocytes
migrating
over
long
distances
along
veins
(lacunae)
toward
site,
where
epidermal
cells
cellular
clusters.
Calcium
oscillations
were
at
near
transiently
affected
by
ruthenium
red,
an
inhibitor
of
calcium
transporters
channels,
red
caused
abnormalities
scales
adult
wings.
These
results
suggest
cell
migration,
cluster
formation,
play
important
roles
scale
development
Ectopic
local
as
a
consequence
evolutionary
co-option
process
for
development.
Tissue
necrosis
is
a
devastating
complication
for
many
human
diseases
and
injuries.
Unfortunately,
our
understanding
of
how
it
impacts
surrounding
healthy
tissue
–
an
essential
consideration
when
developing
effective
methods
to
treat
such
injuries
has
been
limited
by
lack
robust
genetically
tractable
models.
Our
lab
previously
established
method
study
necrosis-induced
regeneration
in
the
Drosophila
wing
imaginal
disc,
which
revealed
unique
phenomenon
whereby
cells
at
distance
from
injury
upregulate
caspase
activity
process
called
Necrosis-induced
Apoptosis
(NiA)
that
vital
regeneration.
Here
we
have
further
investigated
this
phenomenon,
showing
NiA
predominantly
associated
with
highly
regenerative
pouch
region
shaped
genetic
factors
present
presumptive
hinge.
Furthermore,
find
proportion
fail
undergo
apoptosis,
instead
surviving
effector
activation
persist
within
stimulate
reparative
proliferation
late
This
relies
on
initiator
Dronc,
occurs
independent
JNK,
ROS
or
mitogens
characterized
Apoptosis-induced
Proliferation
(AiP)
mechanism.
These
data
reveal
new
means
non-apoptotic
Dronc
signaling
promotes
response
necrotic
damage.
Tissue
necrosis
is
a
devastating
complication
for
many
human
diseases
and
injuries.
Unfortunately,
our
understanding
of
how
it
impacts
surrounding
healthy
tissue
–
an
essential
consideration
when
developing
effective
methods
to
treat
such
injuries
has
been
limited
by
lack
robust
genetically
tractable
models.
Our
lab
previously
established
method
study
necrosis-induced
regeneration
in
the
Drosophila
wing
imaginal
disc,
which
revealed
unique
phenomenon
whereby
cells
at
distance
from
injury
upregulate
caspase
activity
process
called
Necrosis-induced
Apoptosis
(NiA)
that
vital
regeneration.
Here,
we
have
further
investigated
this
phenomenon,
showing
NiA
predominantly
associated
with
highly
regenerative
pouch
region
shaped
genetic
factors
present
presumptive
hinge.
Furthermore,
find
proportion
fail
undergo
apoptosis,
instead
surviving
effector
activation
persist
within
stimulate
reparative
proliferation
late
This
relies
on
initiator
Dronc,
occurs
independent
JNK,
ROS
or
mitogens
characterized
Apoptosis-induced
Proliferation
(AiP)
mechanism.
These
data
reveal
new
means
non-apoptotic
Dronc
signaling
promotes
response
necrotic
damage.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Март 13, 2025
Abstract
The
endocycle
is
a
specialized
cell
cycle
during
which
cells
undergo
repeated
G
/
S
phases
to
replicate
DNA
without
division,
leading
large
polyploid
cells.
transition
from
mitotic
an
can
be
triggered
by
various
stresses,
results
in
unscheduled,
or
induced
endocycling
(iECs).
While
iECs
beneficial
for
wound
healing,
they
also
detrimental
impairing
tissue
growth
promoting
cancer.
However,
the
regulation
of
and
its
role
remain
poorly
understood.
Using
Drosophila
wing
disc
as
model,
we
previously
demonstrated
that
iEC
arrested
through
Jun
N-Terminal
Kinase
(JNK)-dependent,
reversible
senescence-like
response.
it
remains
unclear
how
JNK
activated
impact
overall
structure.
In
this
study,
performed
genetic
screen
identified
Src42A-Shark-Slpr
pathway
upstream
regulator
iECs,
their
arrest.
We
found
tissues
recognize
wounds,
releasing
wound-related
signals
induce
JNK-dependent
developmental
delay.
Similar
closure,
response
triggers
Src-JNK-mediated
actomyosin
remodeling,
yet
persist
rather
than
being
eliminated.
Our
findings
suggest
shares
key
signaling
cytoskeletal
regulatory
mechanisms
with
healing
dorsal
process
embryogenesis.
because
are
retained
within
tissue,
create
unique
system
may
serve
model
studying
chronic
wounds
tumor
progression.
Article
summary
effects
unscheduled
endocycles
on
unclear.
To
investigate
this,
used
switch
analyzed
responses
at
both
structure
levels.
Surprisingly,
recognized
activating
regeneration
remodeling
these
resist
apoptosis,
cleared.
This
persistence
disrupts
normal
revealing
similarities
between
wounds.
has
potential
novel
tumorigenesis.
A
pair
of
eye-antennal
imaginal
discs
give
rise
to
nearly
all
external
structures
the
adult
Drosophila
head
including
compound
eyes,
ocelli,
antennae,
maxillary
palps,
epidermis,
and
bristles.
In
earliest
days
research,
investigators
would
examine
thousands
flies
in
search
viable
mutants
whose
appearance
deviated
from
norm.
The
eyes
are
dispensable
for
viability
perturbations
their
structure
easy
detect.
As
such,
eye
developing
disc
emerged
as
focal
points
studies
genetics
developmental
biology.
Since
few
tools
were
available
at
time,
early
researchers
put
an
enormous
amount
thought
into
models
that
explain
experimental
observations-many
these
hypotheses
remain
be
tested.
However,
"ancient"
have
been
lost
time
no
longer
read
or
incorporated
today's
literature
despite
abundance
field-defining
discoveries
contained
therein.
this
FlyBook
chapter,
I
will
bring
forgotten
classics
together
draw
connections
between
them
modern
tissue
specification
patterning.
doing
so,
hope
a
larger
appreciation
contributions
has
made
our
understanding
development
well
readers'
attention
important
disc.
Armed
with
toolkit
sophisticated
genetic
molecular
methods
using
old
papers
guide,
we
can
use
unravel
mysteries
development.