Notch
signaling
is
an
evolutionarily
conserved
pathway
for
specifying
binary
neuronal
fates,
yet
its
mechanism
remains
elusive.
In
our
accompanying
paper,
using
the
Drosophila
lamina
neurons
(L1-
L5)
as
a
model,
we
show
that
homeodomain
transcription
factor
(HDTF)
Bsh
specifies
L4
and
L5
fates.
Here
test
hypothesis
enables
to
differentially
specify
We
asymmetric
between
newborn
neurons,
but
they
are
not
siblings;
rather,
in
due
Delta
expression
adjacent
L1
neurons.
While
mutually
independent,
necessary
sufficient
fate
over
L5.
With
signaling,
generates
distinct
open
chromatin
landscape
which
results
genome-binding
loci,
leading
L4-specific
gene
transcription.
propose
HDTF
function
integrated
diversify
types.
Frontiers in Molecular Biosciences,
Год журнала:
2024,
Номер
11
Опубликована: Июль 11, 2024
Environmental
conditions
experienced
early
in
the
life
of
an
animal
can
result
gene
expression
changes
later
its
history.
We
have
previously
shown
that
C.
elegans
animals
developmentally
arrested
and
stress
resistant
dauer
stage
(postdauers)
retain
a
cellular
memory
early-life
manifests
during
adulthood
as
genome-wide
expression,
chromatin
states,
altered
history
traits.
One
consequence
developmental
reprogramming
postdauer
adults
is
downregulation
osm-9
TRPV
channel
ADL
chemosensory
neurons
resulting
reduced
avoidance
to
pheromone
component,
ascr#3.
This
response
ascr#3
requires
principal
effector
somatic
nuclear
RNAi
pathway,
Argonaute
(AGO)
NRDE-3.
To
investigate
role
pathway
regulating
due
stress,
we
profiled
mRNA
transcriptome
control
wild-type
nrde-3
mutant
adults.
found
711
differentially
expressed
(DE)
genes
between
neurons,
90%
which
are
dependent
upon
Additionally,
identified
conserved
sequence
enriched
upstream
regulatory
sequences
NRDE-3-dependent
genes.
Surprisingly,
214
DE
considered
“germline-expressed”,
including
21
encoding
Major
Sperm
Proteins
two
sperm-specific
PP1
phosphatases,
GSP-3
GSP-4.
Loss
function
mutations
gsp-3
resulted
both
aberrant
attraction
behaviors.
also
show
AGO
pseudogene,
Y49F6A.1
(
wago-11
),
required
for
avoidance.
Overall,
our
results
suggest
small
RNAs
reproductive
program
their
highlight
nexus
neuronal
networks
calibrating
neuroplasticity.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 15, 2024
A
fundamental
biological
question
is
to
understand
how
cell
types
and
functions
are
determined
by
genomic
proteomic
coding.
basic
form
of
this
ask
if
small
families
genes
or
proteins
code
for
types.
For
example,
it
has
been
shown
that
the
collection
homeodomain
can
uniquely
delineate
all
118
neuron
classes
in
nematode
C.
elegans.
However,
unique
characterization
neither
robust
nor
rare.
Our
goal
paper
develop
a
rigorous
methodology
characterize
molecular
codes.
We
show
fact
information-theoretic
reasons
almost
any
sufficiently
large
able
disambiguate
types,
property
not
noise.
To
quantify
discriminative
properties
codebook
more
refined
way,
we
new
statistics
-
partition
cardinality
entropy
borrowing
ideas
from
coding
theory.
prove
these
data
perturbations,
then
apply
elegans
example
cancer.
In
worm,
transcription
factor
family
distinguished
sparsely
efficiently
compared
control
randomly
selected
genes.
Furthermore,
resolution
type
identities
defined
using
features
increases
as
worm
embryo
develops.
cancer,
perform
pan-cancer
study
where
use
our
interpatient
tumor
heterogeneity
identify
chromosome
containing
HLA
melanoma.
Mapping
neurotransmitter
identities
to
neurons
is
key
understanding
information
flow
in
a
nervous
system.
It
also
provides
valuable
entry
points
for
studying
the
development
and
plasticity
of
neuronal
identity
features.
In
C.
elegans
system,
have
been
largely
assigned
by
expression
pattern
analysis
pathway
genes
that
encode
biosynthetic
enzymes
or
transporters.
However,
many
these
assignments
relied
on
multicopy
reporter
transgenes
may
lack
relevant
cis
-regulatory
therefore
not
provide
an
accurate
picture
usage.
We
analyzed
patterns
16
CRISPR/Cas9-engineered
knock-in
strains
all
main
types
neurotransmitters
(glutamate,
acetylcholine,
GABA,
serotonin,
dopamine,
tyramine,
octopamine)
both
hermaphrodite
male.
Our
reveals
novel
sites
systems
within
glia,
as
well
non-neural
cells.
The
resulting
atlas
defines
be
exclusively
neuropeptidergic,
substantially
expands
repertoire
capable
co-transmitting
multiple
neurotransmitters,
identifies
uptake
monoaminergic
neurotransmitters.
Furthermore,
we
observed
unusual
co-expression
synthesis
genes,
suggesting
existence
transmitters.
results
what
constitutes
most
extensive
whole-animal-wide
map
usage
date,
paving
way
better
communication
specification
.
ABSTRACT
Homeobox
genes
are
among
the
most
deeply
conserved
families
of
transcription
factor-encoding
genes.
Following
their
discovery
in
Drosophila,
homeobox
arrived
on
Caenorhabditis
elegans
stage
with
a
vengeance.
Between
1988
and
1990,
just
few
years
after
initial
flies
vertebrates,
positional
cloning
sequence-based
searches
showed
that
C.
contains
HOX
cluster
genes,
an
apparent
surprise
given
simplicity
non-segmented
body
plan
nematode,
as
well
many
other
non-clustered
all
major
subfamilies
(e.g.
LIM,
POU,
etc.).
Not
quite
40
later,
we
have
exceptionally
deep
understanding
homeodomain
protein
expression
function
elegans,
revealing
prevalent
role
nervous
system
development.
In
this
Spotlight,
provide
historical
perspective
non-comprehensive
journey
through
field
discuss
open
questions
future
directions.
Notch
signaling
is
an
evolutionarily
conserved
pathway
for
specifying
binary
neuronal
fates,
yet
its
mechanism
remains
elusive.
In
our
accompanying
paper,
using
the
Drosophila
lamina
neurons
(L1-
L5)
as
a
model,
we
show
that
homeodomain
transcription
factor
(HDTF)
Bsh
specifies
L4
and
L5
fates.
Here
test
hypothesis
enables
to
differentially
specify
We
asymmetric
between
newborn
neurons,
but
they
are
not
siblings;
rather,
in
due
Delta
expression
adjacent
L1
neurons.
While
mutually
independent,
necessary
sufficient
fate
over
L5.
With
signaling,
generates
distinct
open
chromatin
landscape
which
results
genome-binding
loci,
leading
L4-specific
gene
transcription.
propose
HDTF
function
integrated
diversify
types.