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.
Abstract
The
studies
of
cell
fate
and
lineage
specification
are
fundamental
to
our
understanding
the
development
multicellular
organisms.
Caenorhabditis
elegans
has
been
one
premiere
systems
for
studying
mechanisms
at
single
resolution,
due
its
transparent
nature,
invariant
lineage,
fixed
number
somatic
cells.
We
discuss
general
themes
regulatory
that
have
emerged
from
these
studies,
with
a
focus
on
lineages
fates.
next
review
key
factors
pathways
regulate
discrete
cells
during
embryogenesis
postembryonic
development;
we
transcription
include
numerous
diagrams
depict
expression
specify
embryonic
founder
blast
cells,
diverse
fates
they
generate.
end
by
discussing
some
future
perspectives
in
specification.
Seminars in Cell and Developmental Biology,
Год журнала:
2022,
Номер
152-153, С. 58 - 69
Опубликована: Дек. 7, 2022
The
nervous
system
emerges
from
a
series
of
genetic
programs
that
generate
remarkable
array
neuronal
cell
types.
Each
type
must
acquire
distinct
anatomical
position,
morphology,
and
function,
enabling
the
generation
specialized
circuits
drive
animal
behavior.
How
are
these
diverse
types
patterned
along
anterior-posterior
(A-P)
axis
body?
Hox
genes
encode
transcription
factors
regulate
fate
patterning
events
A-P
system.
While
most
our
understanding
Hox-mediated
control
development
stems
studies
in
segmented
animals
like
flies,
mice,
zebrafish,
important
new
themes
emerging
work
non-segmented
animal:
nematode
Caenorhabditis
elegans.
Studies
C.
elegans
support
idea
needed
continuously
across
different
life
stages
system;
they
not
only
required
dividing
progenitor
cells,
but
also
post-mitotic
neurons
during
adult
life.
In
embryos
young
larvae,
specification,
survival,
migration,
consistent
with
their
neural
roles
other
animals.
late
larvae
adults,
neuron
type-specific
identity
features
critical
for
thereby
extending
functional
repertoire
beyond
early
patterning.
Here,
we
provide
comprehensive
review
To
relate
to
readers
outside
community,
highlight
conserved
invertebrate
vertebrate
We
end
by
calling
attention
functions
paradigmatic
regulators
fate.
Assigning
neurotransmitter
identity
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
features.
Neurotransmitter
identities
have
been
assigned
most
C.
elegans
system
through
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
13
CRISPR/Cas9-engineered
knock-in
strains,
which
report
deployment
all
main
types
neurotransmitters
(glutamate,
acetylcholine,
GABA,
serotonin,
tyramine,
octopamine)
throughout
entire
both
hermaphrodite
male.
Our
reveals
novel
sites
systems
within
glia
defines
be
exclusively
neuropeptidergic.
Furthermore,
we
identified
unusual
combinations
monoaminergic
synthesis
genes,
suggesting
existence
transmitters.
results
what
constitutes
extensive
system-wide
map
usage
date,
paving
way
better
communication
.
ABSTRACT
Terminal
selectors
are
transcription
factors
that
control
neuronal
identity
by
regulating
expression
of
key
effector
molecules,
such
as
neurotransmitter
biosynthesis
proteins
and
ion
channels.
Whether
how
terminal
connectivity
is
poorly
understood.
Here,
we
report
UNC-30
(PITX2/3),
the
selector
GABA
nerve
cord
motor
neurons
in
Caenorhabditis
elegans,
required
for
receptor
clustering,
a
hallmark
postsynaptic
differentiation.
Animals
lacking
unc-30
or
madd-4B,
short
isoform
neuron-secreted
synapse
organizer
madd-4
(punctin/ADAMTSL),
display
severe
type
A
(GABAAR)
clustering
defects
muscle
cells.
Mechanistically,
acts
directly
to
induce
maintain
madd-4B
genes
(e.g.
unc-25/GAD,
unc-47/VGAT).
Hence,
controls
GABAA
cells
presynaptic
cells,
transcriptionally
coordinating
two
crucial
processes
neurotransmission.
Further,
uncover
multiple
target
dual
role
both
an
activator
repressor
gene
transcription.
Our
findings
on
function
may
contribute
our
molecular
understanding
human
conditions,
Axenfeld–Rieger
syndrome,
caused
PITX2
PITX3
variants.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 25, 2024
One
avenue
to
better
understand
brain
evolution
is
map
molecular
patterns
of
evolutionary
changes
in
neuronal
cell
types
across
entire
nervous
systems
distantly
related
species.
Generating
whole-animal
single-cell
transcriptomes
three
nematode
species
from
the
Notch
signaling
is
an
evolutionarily
conserved
pathway
for
specifying
binary
neuronal
fates,
yet
how
it
specifies
different
fates
in
contexts
remains
elusive.
In
our
accompanying
paper,
using
the
Drosophila
lamina
neuron
types
(L1-L5)
as
a
model,
we
show
that
primary
homeodomain
transcription
factor
(HDTF)
Bsh
activates
secondary
HDTFs
Ap
(L4)
and
Pdm3
(L5)
L4/L5
fates.
Here
test
hypothesis
enables
to
differentially
specify
L4
L5
We
asymmetric
between
newborn
neurons,
but
they
are
not
siblings;
rather,
due
Delta
expression
adjacent
L1
neurons.
While
mutually
independent,
necessary
sufficient
fate
over
L5.
The
ON
L4,
compared
OFF
L5,
has
distinct
open
chromatin
landscape
which
allows
bind
genomic
loci,
leading
L4-specific
identity
gene
transcription.
propose
novel
model
integrated
with
HDTF
activity
diversify
by
directly
or
indirectly
generating
constrains
pool
of
genes
can
activate.
Seminars in Cell and Developmental Biology,
Год журнала:
2023,
Номер
154, С. 35 - 47
Опубликована: Июль 11, 2023
Neurons
are
remarkably
long-lived,
non-dividing
cells
that
must
maintain
their
functional
features
(e.g.,
electrical
properties,
chemical
signaling)
for
extended
periods
of
time
–
decades
in
humans.
How
neurons
accomplish
this
incredible
feat
is
poorly
understood.
Here,
we
review
recent
advances,
primarily
the
nematode
C.
elegans,
have
enhanced
our
understanding
molecular
mechanisms
enable
post-mitotic
to
functionality
across
different
life
stages.
We
begin
with
"terminal
selectors"
-
transcription
factors
necessary
establishment
and
maintenance
neuronal
identity.
highlight
new
findings
on
five
terminal
selectors
(CHE-1
[Glass],
UNC-3
[Collier/Ebf1–4],
LIN-39
[Scr/Dfd/Hox4–5],
UNC-86
[Acj6/Brn3a-c],
AST-1
[Etv1/ER81])
from
factor
families
(ZNF,
COE,
HOX,
POU,
ETS).
compare
functions
these
specific
neuron
types
elegans
actions
orthologs
other
invertebrate
(D.
melanogaster)
vertebrate
(M.
musculus)
systems,
highlighting
remarkable
conservation.
Finally,
reflect
implicating
chromatin-modifying
proteins,
such
as
histone
methyltransferases
Polycomb
control
Altogether,
studies
chromatin
modifiers
not
only
shed
light
fundamental
problem
identity
maintenance,
but
also
outline
mechanistic
principles
gene
regulation
may
operate
cell
types.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Фев. 14, 2024
ABSTRACT
Terminal
selectors
are
transcription
factors
that
control
neuronal
identity
by
regulating
the
expression
of
key
effector
molecules,
such
as
neurotransmitter
(NT)
biosynthesis
proteins,
ion
channels
and
neuropeptides.
Whether
how
terminal
connectivity
is
poorly
understood.
Here,
we
report
UNC-30
(PITX2/3),
selector
GABA
motor
neuron
in
C.
elegans
,
required
for
NT
receptor
clustering,
a
hallmark
postsynaptic
differentiation.
Animals
lacking
unc-30
or
madd-4B,
short
isoform
MN-secreted
synapse
organizer
madd-4
(
Punctin/ADAMTSL
),
display
severe
type
A
(GABA
R)
clustering
defects
muscle
cells.
Mechanistically,
acts
directly
to
induce
maintain
madd-4B
genes
(e.g.,
unc-25/GAD
unc-47/VGAT
).
Hence,
controls
R
on
cells
presynaptic
cells,
transcriptionally
coordinating
two
critical
processes
neurotransmission.
Further,
uncover
multiple
target
dual
role
both
an
activator
repressor
gene
transcription.
Our
findings
function
may
contribute
our
molecular
understanding
human
conditions,
Axenfeld-Rieger
syndrome,
caused
PITX2
PITX3
mutations.
