FGF-dependent, polarized SOS activity orchestrates directed migration ofC. elegansmuscle progenitors independently of canonical effectors in vivo
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 14, 2025
Summary
Directed
cell
migration
is
essential
for
animal
development,
tissue
maintenance,
regeneration,
and
disease
states.
Cells
often
migrate
towards,
or
away
from,
sources
of
secreted
signaling
proteins
that
impart
spatial
information.
How
migrating
cells
interpret
extracellular
signals
to
orient
navigate
within
living
animals
a
fundamental
question
in
biology.
Receptor
Tyrosine
Kinase
(RTK)
plays
critical
roles
migration,
aberrant
RTK
pathway
activity
key
driver
multiple
types
cancers.
Yet,
how
RTKs
control
remains
unclear,
part
due
essential,
pleiotropic
development.
To
elucidate
controls
vivo
,
we
used
C.
elegans
muscle
progenitor
as
tractable
system
dissect
temporal
requirements
signal
transduction
cytoskeletal
regulatory
proteins.
Cell
type-specific
depletion
endogenously
tagged
revealed
homologs
FGFR,
GRB2,
SOS,
Ras
independent
their
canonical
ERK,
PI3K,
AKT,
mTOR,
PLCγ
effectors.
Instead,
found
FGF-dependent,
polarized
SOS-1
orients
towards
an
FGF
source,
mislocalizing
SOS
severely
disrupts
ERK.
gain-of-function
experiments
demonstrated
activated
Ras/LET-60
acts
permissively
this
context,
intragenic
revertant
identified
screen
suppressors
Ras/let-60
progenitors
can
be
genetically
uncoupled
from
other
Ras-dependent
developmental
processes.
Our
findings
provide
novel
mechanism
RTK-directed
highlight
the
importance
approaches
mechanisms
physiologically
relevant
contexts.
work
also
outlines
comprehensive
framework
investigating
RTK-dependent
processes
multicellular
organism
introduces
versatile
genetic
toolkit
dissecting
dynamics
homeostasis,
Язык: Английский
Neuronal IL-17 controls Caenorhabditis elegans developmental diapause through CEP-1/p53
Proceedings of the National Academy of Sciences,
Год журнала:
2024,
Номер
121(12)
Опубликована: Март 14, 2024
During
metazoan
development,
how
cell
division
and
metabolic
programs
are
coordinated
with
nutrient
availability
remains
unclear.
Here,
we
show
that
signaled
by
the
neuronal
cytokine,
ILC-17.1,
switches
Caenorhabditis
elegans
development
between
reproductive
growth
dormancy
controlling
activity
of
tumor
suppressor
p53
ortholog,
CEP-1.
Specifically,
upon
food
availability,
ILC-17.1
signaling
amphid
neurons
promotes
glucose
utilization
suppresses
CEP-1/p53
to
allow
growth.
In
absence
is
activated,
up-regulates
cell-cycle
inhibitors,
decreases
phosphofructokinase
cytochrome
C
expression,
causes
larvae
arrest
as
stress-resistant,
quiescent
dauers.
We
propose
a
model
whereby
links
energy
metabolism
cycle
progression
through
CEP-1/p53.
These
studies
describe
ancestral
functions
IL-17
s
family
proteins
relevant
our
understanding
neuroimmune
mechanisms
in
cancer.
They
also
reveal
DNA
damage–independent
function
invertebrate
support
existence
previously
undescribed
C.
dauer
pathway.
Язык: Английский
Metabolic and transcriptomic characterization of summer and winter dormancy in the solitary bee, Osmia lignaria
Insect Biochemistry and Molecular Biology,
Год журнала:
2024,
Номер
166, С. 104074 - 104074
Опубликована: Янв. 14, 2024
The
solitary
bee
Osmia
lignaria
is
a
native
pollinator
in
North
America
with
growing
economic
importance.
life
cycle
of
O.
provides
unique
opportunity
to
compare
the
physiological
and
molecular
mechanisms
underlying
two
ecologically
contrasting
dormancies
within
same
species.
prepupae
become
dormant
during
summer
avoid
high
temperatures.
Shortly
after
adult
eclosion,
they
enter
second
dormancy
overwinter
as
diapausing
adults.
To
these
dormancies,
we
measured
metabolic
rates
gene
expression
across
development
bees
initiate,
maintain,
terminate
both
prepupal
(summer)
(overwintering)
dormancies.
We
observed
moderate
temperature-independent
decrease
gas
exchange
cocoon
spinning
(45
%)
diapause
eclosion
(60
%).
sequenced
assembled
high-quality
reference
genome
from
single
haploid
male
contiguous
n50
5.5
Mbp
facilitate
our
transcriptomic
analysis.
transcriptomes
adults
clustered
into
distinct
groups
more
closely
associated
stage
than
status.
Membrane
transport,
membrane-bound
cellular
components,
oxidoreductase
activity,
glutathione
metabolism,
transcription
factor
activity
increased
diapause,
relative
dormancy.
Further,
groups,
supporting
multiple
phases
winter.
Late
was
profiles
insulin/IGF,
juvenile
hormone,
ecdysone
signaling.
Язык: Английский
RAP-2 and CNH-MAP4 Kinase MIG-15 confer resistance in bystander epithelium to cell-fate transformation by excess Ras or Notch activity
Proceedings of the National Academy of Sciences,
Год журнала:
2024,
Номер
122(1)
Опубликована: Дек. 31, 2024
Induction
of
cell
fates
by
growth
factors
impacts
many
facets
developmental
biology
and
disease.
LIN-3/EGF
induces
the
equipotent
vulval
precursor
cells
(VPCs)
in
Язык: Английский
Exploring the Potential of Lapatinib, Fulvestrant, and Paclitaxel Conjugated with Glycidylated PAMAM G4 Dendrimers for Cancer and Parasite Treatment
Molecules,
Год журнала:
2023,
Номер
28(17), С. 6334 - 6334
Опубликована: Авг. 30, 2023
Fulvestrant
(F),
lapatinib
(L),
and
paclitaxel
(P)
are
hydrophobic,
anticancer
drugs
used
in
the
treatment
of
estrogen
receptor
(ER)
epidermal
growth
factor
(EGFR)-positive
breast
cancer.
In
this
study,
glycidylated
PAMAM
G4
dendrimers,
substituted
with
F,
L,
and/or
P
targeting
tumor
cells,
were
synthesized
characterized,
their
antitumor
activity
against
glioma
U-118
MG
non-small
cell
lung
cancer
A549
cells
was
tested
comparatively
human
non-tumorogenic
keratinocytes
(HaCaT).
All
lines
ER+
EGFR+.
addition,
described
context
antinematode
therapy
on
C.
elegans.
The
results
show
that
water-soluble
conjugates
G4P,
G4F,
G4L,
G4PFL
actively
entered
via
endocytosis
due
to
positive
zeta
potential
(between
13.57–40.29
mV)
nanoparticle
diameter
99–138
nm.
G4P
at
nanomolar
concentrations
most
active,
least
active
conjugate
G4F.
inhibited
proliferation
HaCaT
cells;
cytotoxicity
associated
mainly
damage
(mitochondria
membrane
transport).
toxicity
proportional
number
drug
residues
attached,
exception
G4L;
its
action
two-
eight-fold
stronger
keratinocytes,
respectively,
than
equivalent
alone.
Unfortunately,
non-cancer
sensitive
constructs,
which
forced
a
change
approach
use
ER
EGFR
receptors
as
goal
therapy.
vivo
studies
elegans
have
shown
all
compounds,
notably
G4PFL,
may
be
potentially
useful
anthelmintic
Язык: Английский
Distinct daf-16 isoforms regulate specification of vulval precursor cells in Caenorhabditis elegans.
PubMed,
Год журнала:
2022,
Номер
2022
Опубликована: Янв. 1, 2022
FOXO
transcription
factors
regulate
development,
longevity,
and
stress-resistance
across
species.
The
C.
elegans
ortholog,
daf-16,
has
three
major
isoforms
with
distinct
promoters
N-termini.
Different
combinations
of
different
processes.
Adverse
environments
can
induce
dauer
diapause
after
the
second
larval
molt.
During
dauer,
daf-16
blocks
specification
vulval
precursor
cells,
including
EGFR/Ras-mediated
1˚
fate
LIN-12/Notch-mediated
2˚
specification.
Using
isoform-specific
mutants,
we
find
that
daf-16a
daf-16f
are
functionally
redundant
for
block
to
expression
markers.
In
contrast,
all
contribute
blocking
Язык: Английский