bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Март 2, 2025
SUMMARY
Individual
neurons
have
one
or
more
axons
that
often
extend
long
distances
and
traverse
multiple
microenvironments.
However,
it
is
not
known
how
the
composition
of
individual
established
locally
modulated
to
enable
neuronal
function
plasticity.
Here,
we
use
spatial
translatomics
identify
local
axonal
translatomes
in
anatomically
functionally
specialized
dorsal
root
ganglia
(DRG).
DRG
central
peripheral
opposite
directions
distinct
microenvironments
somatosensation.
Using
Translating
Ribosome
Affinity
Purification
RNA
sequencing,
generated
a
comprehensive
resource
mRNAs
preferentially
translated
within
each
axon.
Locally
proteins
include
pain
receptors,
ion
channels,
translational
machinery,
which
establish
electrophysiologic
properties
regenerative
capacities
for
We
RNA-binding
associated
with
sorting
transporting
related
mRNAs.
These
findings
provide
resources
addressing
translation
shapes
organization
enables
subcellular
neuroplasticity.
HIGHLIGHTS
Distinct
are
localized
axons.
Axonal
govern
capacity,
electrophysiology.
The
RBP,
SFPQ,
coordinates
mRNA
towards
somatosensory
translatome
data
can
be
explored
at
painseq.shinyapps.io/CompartmentTRAP/.
Circulation Research,
Год журнала:
2023,
Номер
132(11), С. 1546 - 1565
Опубликована: Май 25, 2023
The
cardiovascular
system
is
hardwired
to
the
brain
via
multilayered
afferent
and
efferent
polysynaptic
axonal
connections.
Two
major
anatomically
functionally
distinct
though
closely
interacting
subcircuits
within
have
recently
been
defined:
artery-brain
circuit
heart-brain
circuit.
However,
how
nervous
impacts
disease
progression
remains
poorly
understood.
Here,
we
review
recent
findings
on
anatomy,
structures,
inner
workings
of
lesser-known
better-established
We
explore
evidence
that
signals
from
arteries
or
heart
form
a
systemic
finely
tuned
circuit:
inputs
originating
in
arterial
tree
are
conveyed
sensory
neurons
brain.
There,
primary
integration
centers
act
as
hubs
receive
integrate
circuit–derived
process
them
together
with
connections
humoral
cues
distant
regions.
To
conclude
circuit,
transmit
constantly
modified
which
transfer
back
system.
Importantly,
wired
information
secondary
control
wide
variety
traits
encoded
engrams
including
immune
memory,
stress-regulating
hormone
release,
pain,
reward,
emotions,
even
motivated
types
behavior.
Finally,
important
possibility
effector
network
connect
other
peripheral
organs
system,
gut,
liver,
adipose
tissue.
enormous
progress
vis-à-vis
allows
us
propose
novel
neurobiology-centered
hypothesis
term
neuroimmune
hypothesis.
Neuron,
Год журнала:
2023,
Номер
111(11), С. 1776 - 1794.e10
Опубликована: Апрель 6, 2023
Light
touch
sensation
begins
with
activation
of
low-threshold
mechanoreceptor
(LTMR)
endings
in
the
skin
and
propagation
their
signals
to
spinal
cord
brainstem.
We
found
that
clustered
protocadherin
gamma
(Pcdhg)
gene
locus,
which
encodes
22
cell-surface
homophilic
binding
proteins,
is
required
somatosensory
neurons
for
normal
behavioral
reactivity
a
range
tactile
stimuli.
Developmentally,
distinct
Pcdhg
isoforms
mediate
LTMR
synapse
formation
through
neuron-neuron
interactions
peripheral
axonal
branching
neuron-glia
interactions.
The
Pcdhgc3
isoform
mediates
between
sensory
axons
promote
vivo
sufficient
induce
postsynaptic
specializations
vitro.
Moreover,
loss
Pcdhgs
synaptic
inputs
dorsal
horn
leads
fewer
corticospinal
synapses
on
neurons.
These
findings
reveal
essential
roles
diversity
neuron
formation,
branching,
stepwise
assembly
central
mechanosensory
circuitry.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Март 12, 2024
Abstract
The
ascending
somatosensory
pathways
convey
crucial
information
about
pain,
touch,
itch,
and
body
part
movement
from
peripheral
organs
to
the
central
nervous
system.
Despite
a
significant
need
for
effective
therapeutics
modulating
pain
other
modalities,
clinical
translation
remains
challenging,
which
is
likely
related
species-specific
features
lack
of
in
vitro
models
directly
probe
manipulate
this
polysynaptic
pathway.
Here,
we
established
human
assembloids
(hASA)–
four-part
assembloid
completely
generated
pluripotent
stem
cells
that
integrates
somatosensory,
spinal,
diencephalic,
cortical
organoids
model
spinothalamic
Transcriptomic
profiling
confirmed
presence
key
cell
types
circuit.
Rabies
tracing
calcium
imaging
showed
sensory
neurons
connected
with
dorsal
spinal
cord
projection
neurons,
axons
further
thalamic
neurons.
Following
noxious
chemical
stimulation,
single
neuron
intact
hASA
demonstrated
coordinated
response,
while
concomitant
extracellular
recordings
revealed
synchronized
activity
across
assembloid.
Loss
sodium
channel
SCN9A,
causes
insensitivity
humans,
disrupted
synchrony
hASA.
Taken
together,
these
experiments
demonstrate
ability
functionally
assemble
essential
components
These
findings
could
both
accelerate
our
understanding
circuits
facilitate
therapeutic
development.
Somatosensory
pathways
convey
crucial
information
about
pain,
touch,
itch
and
body
part
movement
from
peripheral
organs
to
the
central
nervous
system1,2.
Despite
substantial
needs
understand
how
these
assemble
develop
pain
therapeutics,
clinical
translation
remains
challenging.
This
is
probably
related
species-specific
features
lack
of
in
vitro
models
polysynaptic
pathway.
Here
we
established
a
human
ascending
somatosensory
assembloid
(hASA),
four-part
generated
pluripotent
stem
cells
that
integrates
somatosensory,
spinal,
thalamic
cortical
organoids
model
spinothalamic
Transcriptomic
profiling
confirmed
presence
key
cell
types
this
circuit.
Rabies
tracing
calcium
imaging
showed
sensory
neurons
connect
dorsal
spinal
cord
neurons,
which
further
neurons.
Following
noxious
chemical
stimulation,
hASA
demonstrated
coordinated
response.
In
addition,
extracellular
recordings
revealed
synchronized
activity
across
assembloid.
Notably,
loss
sodium
channel
NaV1.7,
causes
insensitivity,
disrupted
synchrony
hASA.
By
contrast,
gain-of-function
SCN9A
variant
associated
with
extreme
disorder
induced
hypersynchrony.
These
experiments
ability
functionally
essential
components
pathway,
could
accelerate
our
understanding
circuits
facilitate
therapeutic
development.
Abstract
Since
the
days
of
Ramón
y
Cajal,
vast
diversity
neuronal
and
particularly
dendrite
morphology
has
been
used
to
catalog
neurons
into
different
classes.
Dendrite
varies
greatly
reflects
functions
performed
by
types
neurons.
Significant
progress
made
in
our
understanding
how
dendrites
form
molecular
factors
forces
that
shape
these
often
elaborately
sculpted
structures.
Here,
we
review
work
nematode
Caenorhabditis
elegans
shed
light
on
developmental
mechanisms
mediate
morphogenesis
with
a
focus
studies
investigating
ciliated
sensory
highly
elaborated
dendritic
trees
somatosensory
These
studies,
which
combine
time-lapse
imaging,
genetics,
biochemistry,
reveal
an
intricate
network
function
both
intrinsically
extrinsically
from
surrounding
tissues.
Therefore,
is
result
multiple
tissue
interactions,
ultimately
determine
arbors.
Global Change Biology,
Год журнала:
2024,
Номер
30(9)
Опубликована: Сен. 1, 2024
Abstract
Anthropogenically
induced
changes
to
the
natural
world
are
increasingly
exposing
organisms
stimuli
and
stress
beyond
that
which
they
adapted.
In
aquatic
systems,
it
is
thought
certain
life
stages
more
vulnerable
than
others,
with
embryos
being
flagged
as
highly
susceptible
environmental
stressors.
Interestingly,
evidence
from
across
a
wide
range
of
taxa
suggests
can
hatch
prematurely,
potentially
an
adaptive
response
external
stressors,
despite
potential
for
individual
costs
linked
underdeveloped
behavioural
and/or
physiological
functions.
However,
surprisingly
little
research
has
investigated
prevalence,
causes
consequences
premature
hatching,
no
compilation
literature
exists.
Here,
we
review
what
known
about
hatching
in
discuss
how
this
phenomenon
likely
become
exacerbated
anthropogenically
global
change.
Specifically,
(1)
mechanisms
including
triggers
experimental
systems;
(2)
implications
at
different
levels
biological
organisation
individuals
ecosystems;
(3)
outline
knowledge
gaps
future
directions
understanding
drivers
hatching.
We
found
prematurely
broad
abiotic
(i.e.
temperature,
oxygen,
toxicants,
light,
pH,
salinity)
biotic
predators,
pathogens)
also
provide
empirical
appears
be
common
rapid
thermal
ramping
fish
species.
argue
represents
fascinating
yet
untapped
area
study,
may
some
additional
resilience
communities
face
ongoing
Journal of Biomedical Science,
Год журнала:
2023,
Номер
30(1)
Опубликована: Март 6, 2023
Abstract
E26
transformation-specific
(ETS)
transcription
variant
5
(ETV5),
also
known
as
ETS-related
molecule
(ERM),
exerts
versatile
functions
in
normal
physiological
processes,
including
branching
morphogenesis,
neural
system
development,
fertility,
embryonic
immune
regulation,
and
cell
metabolism.
In
addition,
ETV5
is
repeatedly
found
to
be
overexpressed
multiple
malignant
tumors,
where
it
involved
cancer
progression
an
oncogenic
factor.
Its
roles
metastasis,
proliferation,
oxidative
stress
response
drug
resistance
indicate
that
a
potential
prognostic
biomarker,
well
therapeutic
target
for
treatment.
Post-translational
modifications,
gene
fusion
events,
sophisticated
cellular
signaling
crosstalk
non-coding
RNAs
contribute
the
dysregulation
abnormal
activities
of
ETV5.
However,
few
studies
date
systematically
summarized
role
molecular
mechanisms
benign
diseases
progression.
this
review,
we
specify
structure
post-translational
modifications
its
critical
are
draw
panorama
specialists
clinicians.
The
updated
biology
tumor
delineated.
Finally,
prospect
further
direction
research
oncology
translational
applications
clinic.