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.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Aug. 22, 2024
Adult
zebrafish
fins
regenerate
to
their
original
size
regardless
of
damage
extent,
providing
a
tractable
model
organ
and
scale
control.
Gain-of-function
voltage-gated
K
+
channels
expressed
in
fibroblast-lineage
blastema
cells
promotes
excessive
fin
outgrowth,
leading
long-finned
phenotype.
Similarly,
inhibition
the
Ca
2+
-dependent
phosphatase
calcineurin
during
regeneration
causes
dramatic
overgrowth.
However,
fluxes
potential
origins
from
dynamic
membrane
voltages
have
not
been
explored
or
linked
restoration.
We
used
GCaMP
imaging
regenerating
adult
identify
heterogeneous
transients
distal
cells.
Membrane
depolarization
isolated
fibroblasts
triggered
spikes
dependent
on
channel
activity.
Single
cell
transcriptomics
identified
cacna1c
(L-type
channel),
cacna1ba
(N-type),
cacna1g
(T-type)
as
candidate
mediators
signaling.
Small
molecule
revealed
L-
and/or
N-type
act
regenerative
outgrowth
restore
scale.
Strikingly,
homozygous
mutant
regenerated
extraordinarily
long
due
prolonged
outgrowth.
The
far
exceeded
length
but
with
otherwise
normal
ray
skeletons.
Therefore,
mutants
uniquely
provide
genetic
loss-of-function
that
decouples
developmental
Live
showed
T-type
Cacna1g
enable
dynamics
blastemal
mesenchyme
phase.
conclude
"bioelectricity"
for
control
likely
entirely
reflects
voltage-modulated
specifically
steadily
decelerates
at
rate
tuned
size.
iScience,
Journal Year:
2024,
Volume and Issue:
27(9), P. 110737 - 110737
Published: Aug. 23, 2024
Highlights•Amputation
position
changes
tissue-wide
proliferation
response•Regeneration
deploys
transient
regeneration-activated
cell
states•Sqstm1
slows
down
regenerative
outgrowth
in
distal
injuries•Prediction:
positional
information
is
transduced
by
ECM
during
regenerationSummaryInjury
common
the
life
of
organisms.
Because
extent
damage
cannot
be
predicted,
injured
organisms
must
determine
how
much
tissue
needs
to
restored.
Although
it
known
that
amputation
affects
regeneration
speed
appendages,
mechanisms
conveying
remain
unclear.
We
investigated
dynamics
regenerating
caudal
fins
African
killifish
(Nothobranchius
furzeri)
and
found
position-specific,
differential
spatial
distribution
modulation,
persistence,
magnitude
proliferation.
Single-cell
RNA
sequencing
revealed
a
state
(TRACS)
basal
epidermis
amplified
match
given
expresses
components
modifiers
extracellular
matrix
(ECM).
Notably,
CRISPR-Cas9-mediated
deletion
modifier
sequestosome
1
(sqstm1)
increased
capacity
injuries,
suggesting
growth
rate
can
uncoupled
from
position.
propose
TRACS
transduce
blastema
remodeling
ECM.Graphical
abstract
Frontiers in Ecology and Evolution,
Journal Year:
2021,
Volume and Issue:
9
Published: March 25, 2021
The
capacity
of
regenerating
a
new
structure
after
losing
an
old
one
is
major
challenge
in
the
animal
kingdom.
Fish
have
emerged
as
interesting
model
to
study
regeneration
due
their
high
and
diverse
regenerative
capacity.
To
date,
most
efforts
focused
on
revealing
mechanisms
underlying
fin
regeneration,
but
information
why
how
this
evolves
remains
incomplete.
Here,
we
propose
livebearing
fish
family
Poeciliidae
promising
system
evolution
regeneration.
First,
review
current
state
knowledge
kingdom,
with
special
emphasis
fins.
Second,
summarize
recent
advances
our
understanding
behind
fish.
Third,
discuss
potential
evolutionary
pressures
that
may
modulate
fins
three
theories
for
natural
sexual
selection
can
lead
regeneration:
(1)
signaling-driven
(2)
predation-driven
(3)
matrotrophy-suppressed
Finally,
argue
from
are
excellent
test
these
theories,
because
they
comprise
large
variety
species
well-defined
phylogenetic
framework
inhabit
very
different
environments
display
remarkable
variation
reproductive
traits,
allowing
comparative
studies
among
closely
related
species,
populations
within
or
individuals
populations.
This
has
shed
light
genetic
molecular
driving
diversification
vertebrates.
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.
