bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2021,
Volume and Issue:
unknown
Published: Jan. 3, 2021
Abstract
Pleiotropy
caused
by
single-gene
mutations
is
common
and
poorly
understood.
A
zebrafish
null
mutant
of
DNA
polymerase
α
subunit
B,
huli
hutu
(
hht)
,
evolves
a
complex
pleiotropy
associated
with
damage
S
phase
arrest
across
multiple
organ
systems
over
5-7
days,
including
nuclear
atypia,
cellular
feature
in
human
cancers
pre-cancers,
gastrointestinal
organs,
fragmentation
the
eye
brain.
The
pleiotropic
pattern
hht
phenotypes
explained
progressive
loss
wild-type
maternal
pola2
function
homozygous
embryos
whose
mRNA
becomes
undetectable
24
hours
post-fertilization
(hpf).
Inhibition
synthesis
aphidicolin
or
hydroxyurea
from
hpf
phenocopied
.
These
results
are
consistent
model
which
time-sensitive,
reduced
capacity
for
cell
death
fast-replicating
cells,
atypia
tissues
fewer
larger
cells.
Jellyfish,
with
their
tetraradial
symmetry,
offer
a
novel
paradigm
for
addressing
patterning
mechanisms
during
regeneration.
Here
we
show
that
an
interplay
between
mechanical
forces,
cell
migration
and
proliferation
allows
jellyfish
fragments
to
regain
shape
functionality
rapidly,
notably
by
efficient
restoration
of
the
central
feeding
organ
(manubrium).
Fragmentation
first
triggers
actomyosin-powered
remodeling
restores
body
umbrella
shape,
causing
radial
smooth
muscle
fibers
converge
around
‘hubs’
which
serve
as
positional
landmarks.
Stabilization
these
hubs,
associated
expression
Wnt6
,
depends
on
configuration
adjoining
fiber
‘spokes’.
Stabilized
hubs
presage
site
manubrium
blastema,
whose
growth
is
Wnt/β-catenin
dependent
fueled
both
long-range
recruitment.
Manubrium
morphogenesis
modulated
its
connections
gastrovascular
canal
system.
We
conclude
in
regenerating
emerges
mainly
from
local
interactions,
triggered
directed
process.
Proceedings of the National Academy of Sciences,
Journal Year:
2023,
Volume and Issue:
120(21)
Published: May 15, 2023
Processes
that
regulate
size
and
patterning
along
an
axis
must
be
highly
integrated
to
generate
robust
shapes;
relative
changes
in
these
processes
underlie
both
congenital
disease
evolutionary
change.
Fin
length
mutants
zebrafish
have
provided
considerable
insight
into
the
pathways
regulating
fin
size,
yet
signals
underlying
remained
less
clear.
The
bony
rays
of
fins
possess
distinct
proximodistal
axis,
reflected
location
ray
bifurcations
lengths
segments,
which
show
progressive
shortening
axis.
Here,
we
thyroid
hormone
(TH)
regulates
aspects
caudal
rays,
regardless
size.
TH
promotes
distal
gene
expression
patterns,
coordinating
segment
with
skeletal
outgrowth
This
distalizing
role
for
is
conserved
between
development
regeneration,
all
(paired
medial),
Danio
species
as
well
distantly
related
medaka.
During
regenerative
outgrowth,
acutely
induces
Shh-mediated
bifurcation.
Zebrafish
multiple
nuclear
receptors,
found
unliganded
Thrab-but
not
Thraa
or
Thrb-inhibits
formation
features.
Broadly,
results
demonstrate
morphology
regulated
independently
from
size-instructive
signals.
Modulating
size-either
through
metabolism
other
hormone-independent
pathways-can
shift
ways
recapitulate
diversity
nature.
Frontiers in Cell and Developmental Biology,
Journal Year:
2020,
Volume and Issue:
8
Published: Oct. 20, 2020
The
diversity
of
regenerative
phenomena
seen
in
adult
metazoans,
as
well
their
underlying
mechanistic
bases,
are
still
far
from
being
comprehensively
understood.
Reviewing
both
ultrastructural
and
molecular
data,
the
present
work
aims
to
showcase
increasing
relevance
invertebrate
deuterostomes,
i.e.,
echinoderms,
hemichordates,
cephalochordates
tunicates,
invaluable
models
study
cellular
aspects
regeneration.
Our
comparative
approach
suggests
a
fundamental
contribution
local
dedifferentiation
-rather
than
mobilization
resident
undifferentiated
stem
cells-
an
important
mechanism
contributing
regeneration
these
groups.
Thus,
elucidating
origins,
recruitment
fate
cells,
signals
underpinning
tissue
regrowth
regeneration-competent
will
provide
foundation
for
future
research
tackling
relatively
limited
abilities
vertebrates,
with
clear
applications
medicine.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Oct. 28, 2023
Abstract
Upon
limb
amputation
in
salamanders,
anterior
and
posterior
connective
tissue
cells
form
distinct
signalling
centres
that
together
fuel
successful
regeneration.
The
molecular
properties
distinguish
prior
to
injury,
which
enable
them
initiate
different
after
amputation,
are
not
known.
These
identities,
crucial
for
regeneration,
were
thought
be
established
during
development
persist
through
successive
regeneration
cycles
as
positional
memory.
However,
the
nature
of
these
memory
states
whether
identities
can
engineered
have
remained
outstanding
questions.
Here,
we
identify
a
positive
feedback
mechanism
encoding
identity
axolotl
limb,
used
newly
encode
regenerative
cells.
Posterior
express
residual
levels
bHLH
transcription
factor
Hand2
from
this
is
priming
molecule
necessary
sufficient
establish
Shh
centre
amputation.
During
feeds
back
reinforces
expression
nearby
sustained
following
safeguarding
memory,
while
shut
off.
As
consequence
Hand2-Shh
system,
differentially
susceptible
alteration.
stabilised
against
anteriorisation
their
poises
trigger
loop.
In
contrast,
reprogrammed:
transient
exposure
causes
gain
lasting
competence
.
way,
an
opportunity
entry
point
re-write
Our
results
implicate
stability
explain
why
more
easily
altered
one
direction
(anterior
posterior)
than
other.
Because
modifying
changes
outputs
cells,
our
findings
wider
implications
engineering.
Abstract
Faithful
establishment
and
maintenance
of
proportion
is
seen
across
biological
systems
provides
a
glimpse
at
fundamental
rules
scaling
that
underlie
development
evolution.
Dysregulation
observed
in
range
human
diseases
growth
disorders,
indicating
proper
an
essential
component
normal
anatomy
physiology.
However,
when
viewed
through
evolutionary
lens,
shifts
the
regulation
relative
are
one
most
striking
sources
morphological
diversity
among
organisms.
To
date,
mechanisms
via
which
specified
maintained
remain
unclear.
Through
application
powerful
experimental,
genetic
molecular
approaches,
teleost
fin
has
provided
effective
model
to
investigate
scaling,
size,
vertebrate
This
article
categorized
under:
Establishment
Spatial
Temporal
Patterns
>
Regulation
Size,
Proportion,
Timing
Adult
Stem
Cells,
Tissue
Renewal,
Regeneration
Comparative
Development
Evolution
Organ
Diversity
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: March 31, 2024
Summary
Injury
is
a
common
occurrence
in
the
life
of
organisms.
Because
extent
damage
cannot
be
predicted,
injured
organisms
must
determine
how
much
tissue
needs
to
restored.
It
known
that
amputation
position
determines
regeneration
speed
amputated
appendages
regeneration-competent
animals.
Yet,
it
not
clear
positional
information
conveyed
during
regeneration.
Here,
we
investigated
dynamics
regenerating
caudal
fins
African
killifish
(
Nothobranchius
furzeri
).
We
report
position-specific,
differential
modulation
spatial
distribution,
duration,
and
magnitude
proliferation.
Regenerating
profiled
by
single
cell
RNA
sequencing
identified
Transient
Regeneration-Activated
Cell
State
(TRACS)
amplified
match
given
position.
located
this
TRACS
basal
epidermis
found
them
express
components
modifiers
extracellular
matrix
(ECM).
propose
role
for
these
cells
transducing
blastema
remodeling
ECM.
Highlights
Amputation
changes
tissue-wide
proliferation
response
Transcriptional
compartmentalization
relative
injury
type
Regeneration
deploys
States
Prediction:
transduced
ECM