bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Июнь 15, 2023
Abstract
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.
Abstract
Animals
rely
on
their
nervous
systems
to
process
sensory
inputs,
integrate
these
with
internal
signals,
and
produce
behavioral
outputs.
This
is
enabled
by
the
highly
specialized
morphologies
functions
of
neurons.
Neuronal
cells
share
multiple
structural
physiological
features,
but
they
also
come
in
a
large
diversity
types
or
classes
that
give
system
its
broad
range
plasticity.
diversity,
first
recognized
over
century
ago,
spurred
classification
efforts
based
morphology,
function,
molecular
criteria.
Caenorhabditis
elegans,
precisely
mapped
at
anatomical
level,
an
extensive
description
most
neurons,
genetic
amenability,
has
been
prime
model
for
understanding
how
neurons
develop
diversify
mechanistic
level.
Here,
we
review
gene
regulatory
mechanisms
driving
neurogenesis
diversification
neuron
subclasses
C.
elegans.
We
discuss
our
current
specification
neuronal
progenitors
differentiation
terms
transcription
factors
involved
ensuing
changes
expression
chromatin
landscape.
The
central
theme
emerged
identity
defined
modules
batteries
are
under
control
parallel
yet
interconnected
mechanisms.
focus
how,
achieve
terminal
identities,
information
along
developmental
lineages.
Moreover,
diversified
postembryonically
time-,
sex-,
activity-dependent
manner.
Finally,
development
can
provide
insights
into
evolution
diversity.
In
both
invertebrates
such
as
Drosophila
and
vertebrates
mouse
or
human,
the
brain
contains
most
diverse
population
of
cell
types
any
tissue.
It
is
generally
accepted
that
transcriptional
diversity
an
early
step
in
generating
neuronal
glial
diversity,
followed
by
establishment
a
unique
gene
expression
profile
determines
morphology,
connectivity,
function.
,
there
are
two
neural
stem
cells,
called
Type
1
(T1)
2
(T2)
neuroblasts.
contrast
to
T1
neuroblasts,
T2
neuroblasts
generate
intermediate
progenitors
(INPs)
expand
number
types.
The
T2-derived
neurons
contributes
large
portion
central
complex
(CX),
conserved
region
plays
role
sensorimotor
integration.
Recent
work
has
revealed
much
connectome
CX,
but
how
this
assembled
remains
unclear.
Mapping
derived
from
necessary
linking
assembly
adult
brain.
Here
we
perform
single
nuclei
RNA
sequencing
neuroblast-derived
glia.
We
identify
clusters
containing
all
known
classes
glia,
male/female
enriched,
161
neuron-specific
clusters.
map
neurotransmitter
neuropeptide
transcription
factor
combinatorial
codes
for
each
cluster
(presumptive
neuron
subtype).
This
directs
functional
studies
determine
whether
code
specifies
distinct
type
within
CX.
several
columnar
subtypes
(NPF+
AstA+)
closely
related
Our
data
support
hypothesis
represents
one
few
subtypes.
In
both
invertebrates
such
as
Drosophila
and
vertebrates
mouse
or
human,
the
brain
contains
most
diverse
population
of
cell
types
any
tissue.
It
is
generally
accepted
that
transcriptional
diversity
an
early
step
in
generating
neuronal
glial
diversity,
followed
by
establishment
a
unique
gene
expression
profile
determines
morphology,
connectivity,
function.
,
there
are
two
neural
stem
cells,
called
Type
1
(T1)
2
(T2)
neuroblasts.
contrast
to
T1
neuroblasts,
T2
neuroblasts
generate
intermediate
progenitors
(INPs)
expand
number
types.
The
T2-derived
neurons
contributes
large
portion
central
complex
(CX),
conserved
region
plays
role
sensorimotor
integration.
Recent
work
has
revealed
much
connectome
CX,
but
how
this
assembled
remains
unclear.
Mapping
derived
from
necessary
linking
assembly
adult
brain.
Here
we
perform
single
nuclei
RNA
sequencing
neuroblast-derived
glia.
We
identify
clusters
containing
all
known
classes
glia,
male/female
enriched,
161
neuron-specific
clusters.
map
neurotransmitter
neuropeptide
transcription
factor
combinatorial
codes
for
each
cluster
(presumptive
neuron
subtype).
This
directs
functional
studies
determine
whether
code
specifies
distinct
type
within
CX.
several
columnar
subtypes
(NPF+
AstA+)
closely
related
Our
data
support
hypothesis
represents
one
few
subtypes.
In
both
Drosophila
and
mammals,
the
brain
contains
most
diverse
population
of
cell
types
any
tissue.
It
is
generally
accepted
that
transcriptional
diversity
an
early
step
in
generating
neuronal
glial
diversity,
followed
by
establishment
a
unique
gene
expression
profile
determines
morphology,
connectivity,
function.
,
there
are
two
neural
stem
cells,
called
Type
1
(T1)
2
(T2)
neuroblasts.
The
T2-derived
neurons
contributes
large
portion
central
complex
(CX),
conserved
region
plays
role
sensorimotor
integration.
Recent
work
has
revealed
much
connectome
CX,
but
how
this
assembled
remains
unclear.
Mapping
necessary
linking
to
assembly
adult
brain.
Here
we
perform
single
nuclei
RNA
sequencing
T2
neuroblast-derived
glia.
We
identify
clusters
containing
all
known
classes
glia,
male/female
enriched,
161
neuron-specific
clusters.
map
neurotransmitter
neuropeptide
transcription
factor
combinatorial
codes
for
each
cluster.
This
directs
functional
studies
determine
whether
code
specifies
distinct
neuron
type
within
CX.
several
columnar
subtypes
(NPF+
AstA+)
closely
related
Our
data
support
hypothesis
cluster
represents
one
or
few
subtypes.
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.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Дек. 11, 2023
Abstract
In
both
invertebrates
such
as
Drosophila
and
vertebrates
mouse
or
human,
the
brain
contains
most
diverse
population
of
cell
types
any
tissue.
It
is
generally
accepted
that
transcriptional
diversity
an
early
step
in
generating
neuronal
glial
diversity,
followed
by
establishment
a
unique
gene
expression
profile
determines
morphology,
connectivity,
function.
,
there
are
two
neural
stem
cells,
called
Type
1
(T1)
2
(T2)
neuroblasts.
contrast
to
T1
neuroblasts,
T2
neuroblasts
generate
intermediate
progenitors
(INPs)
expand
number
types.
The
T2-derived
neurons
contributes
large
portion
central
complex
(CX),
conserved
region
plays
role
sensorimotor
integration.
Recent
work
has
revealed
much
connectome
CX,
but
how
this
assembled
remains
unclear.
Mapping
derived
from
necessary
linking
assembly
adult
brain.
Here
we
perform
single
nuclei
RNA
sequencing
neuroblast-derived
glia.
We
identify
clusters
containing
all
known
classes
glia,
male/female
enriched,
161
neuron-specific
clusters.
map
neurotransmitter
neuropeptide
transcription
factor
combinatorial
codes
for
each
cluster
(presumptive
neuron
subtype).
This
directs
functional
studies
determine
whether
code
specifies
distinct
type
within
CX.
several
columnar
subtypes
(NPF+
AstA+)
closely
related
Our
data
support
hypothesis
represents
one
few
subtypes.
Drosophila
nervous
system
development
progresses
through
a
series
of
well-characterized
steps
in
which
homeodomain
transcription
factors
(HDTFs)
play
key
roles
during
most,
if
not
all,
phases.
Strikingly,
although
some
HDTFs
have
only
one
role,
many
others
are
involved
multiple
the
developmental
process.
Most
engaged
conserved
vertebrates
and
often
similar
vertebrate
development.
In
this
Spotlight,
we
focus
on
role
embryogenesis,
where
they
were
first
characterized.
Communications Biology,
Год журнала:
2024,
Номер
7(1)
Опубликована: Апрель 27, 2024
Abstract
Our
nervous
system
contains
billions
of
neurons
that
form
precise
connections
with
each
other
through
interactions
between
cell
surface
proteins.
In
Drosophila
,
the
Dpr
and
DIP
immunoglobulin
protein
subfamilies
homophilic
or
heterophilic
to
instruct
synaptic
connectivity,
growth,
survival.
However,
upstream
regulatory
mechanisms
Dprs
DIPs
are
not
clear.
On
hand,
while
transcription
factors
have
been
implicated
in
target
recognition,
their
downstream
proteins
remain
mostly
unknown.
We
conduct
an
F1
dominant
modifier
genetic
screen
identify
regulators
DIPs.
huckebein
(
hkb
),
a
factor
previously
recognition
dorsal
Is
motor
neuron.
show
genetically
interacts
DIP-α
loss
leads
complete
removal
expression
specifically
neurons.
then
confirm
this
specificity
is
neuron
specific
factor,
even-skipped
eve
which
acts
.
Analysis
interaction
reveals
they
act
same
pathway
regulate
connectivity.
study
provides
insight
into
transcriptional
regulation
suggests
distinct
exist
for
CSP
different
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 4, 2024
KDM5
family
proteins
are
best
known
for
their
demethylation
of
the
promoter
proximal
chromatin
mark
H3K4me3.
KDM5-regulated
transcription
is
critical
in
brain,
with
variants
X-linked
paralog
