Current Biology,
Journal Year:
2024,
Volume and Issue:
34(3), P. R102 - R116
Published: Feb. 1, 2024
Precise
synaptic
connectivity
is
a
prerequisite
for
the
function
of
neural
circuits,
yet
individual
neurons,
taken
out
their
developmental
context,
readily
form
unspecific
synapses.
How
does
genome
encode
brain
wiring
in
light
this
apparent
contradiction?
Synaptic
specificity
outcome
long
series
processes
and
mechanisms
before,
during
after
synapse
formation.
much
promiscuity
permissible
or
necessary
at
moment
partner
choice
depends
on
extent
to
which
prior
development
restricts
available
partners
subsequent
corrects
initially
made
can
thereby
play
important
roles
precise
connectivity,
but
also
facilitate
flexibility
robustness.
In
review,
we
assess
experimental
evidence
prevalence
promiscuous
formation
development.
Many
well-established
approaches
are
based
genetic
perturbation
an
assessment
only
adult;
make
it
difficult
pinpoint
when
given
defect
mechanism
occurred.
many
cases,
such
studies
reveal
that
restrict
availability
already
Subsequently,
choice,
factors
including
competency,
interaction
dynamics
molecular
recognition
further
partners.
The
discussion
through
lens
suggests
algorithmic
process
neurons
capable
continuously
prevented
from
making
wrong
choices,
with
no
single
time
point
sufficient
explain
outcome.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Oct. 13, 2023
A
catalog
of
neuronal
cell
types
has
often
been
called
a
"parts
list"
the
brain,
and
regarded
as
prerequisite
for
understanding
brain
function.
In
optic
lobe
Cell Reports,
Journal Year:
2024,
Volume and Issue:
43(2), P. 113798 - 113798
Published: Feb. 1, 2024
Neurons
establish
specific
synapses
based
on
the
adhesive
properties
of
cell-surface
proteins
while
also
retaining
ability
to
form
in
a
relatively
non-selective
manner.
However,
comprehensive
understanding
underlying
mechanism
reconciling
these
opposing
characteristics
remains
incomplete.
Here,
we
have
identified
Side-IV/Beat-IIb,
members
Drosophila
immunoglobulin
superfamily,
as
combination
recognition
molecules
inducing
synapse
formation.
The
Side-IV/Beat-IIb
transduces
bifurcated
signaling
with
Side-IV's
co-receptor,
Kirre,
and
synaptic
scaffold
protein,
Dsyd-1.
Genetic
experiments
subcellular
protein
localization
analyses
showed
Side-IV/Beat-IIb/Kirre/Dsyd-1
complex
two
essential
functions.
First,
it
narrows
neuronal
binding
specificity
through
extracellular
interactions.
Second,
recruits
formation
factors,
Kirre
Dsyd-1,
restrict
loci
inhibit
miswiring.
This
dual
function
explains
how
combinations
enable
ranking
preferred
interactions
among
pairs
achieve
circuits
vivo.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 4, 2025
Abstract
Animal
behaviors
are
executed
by
motor
neurons
(MNs),
which
receive
information
from
complex
pre-motor
neuron
(preMN)
circuits
and
output
commands
to
muscles.
How
established
during
development
remains
an
important
unsolved
problem
in
neuroscience.
Here
we
focus
on
the
of
that
control
movements
adult
legs
Drosophila
melanogaster
.
After
generating
single-cell
RNA
sequencing
(scRNAseq)
datasets
for
leg
MNs
at
multiple
time
points,
describe
course
gene
expression
families.
This
analysis
reveals
transcription
factors
(TFs)
cell
adhesion
molecules
(CAMs)
appear
drive
molecular
diversity
between
individual
MNs.
In
parallel,
introduce
ConnectionMiner,
a
novel
computational
tool
integrates
scRNAseq
data
with
electron
microscopy-derived
connectomes.
ConnectionMiner
probabilistically
refines
ambiguous
type
annotations
leveraging
neural
wiring
patterns,
and,
turn,
it
identifies
combinatorial
signatures
correlate
synaptic
connectivity
strength.
Applied
system,
yields
comprehensive
transcriptional
annotation
both
preMNs
uncovers
candidate
effector
combinations
likely
orchestrate
assembly
ultimately
Understanding
the
developmental
changes
in
neuronal
lineages
is
crucial
to
elucidate
how
they
assemble
into
functional
neural
networks.
Studies
investigating
nervous
system
development
model
systems
have
focused
on
only
a
few
regions
of
central
due
limited
availability
genetic
drivers
that
target
specific
throughout
and
adult
life.
This
has
hindered
our
understanding
distinct
interconnect
form
circuits
during
development.
Here,
we
present
split-GAL4
library
composed
driver
lines,
which
generated
via
editing
genomic
locus
lineage-specific
transcription
factors
demonstrate
can
use
this
specifically
most
individual
hemilineages
Drosophila
ventral
nerve
cord
(VNC)
adulthood.
Using
these
found
striking
morphological
processes
within
lineage
metamorphosis.
We
also
demonstrated
neurochemical
features
classes
be
quickly
assessed.
Lastly,
documented
behaviors
elicited
response
optogenetic
activation
comprehensive
lineage-behavior
map
entire
fly
VNC.
Looking
forward,
will
provide
tools
needed
address
questions
emerging
from
analysis
recent
VNC
connectome
transcriptome
datasets.
Understanding
the
developmental
changes
in
neuronal
lineages
is
crucial
to
elucidate
how
they
assemble
into
functional
neural
networks.
Studies
investigating
nervous
system
development
model
systems
have
focused
on
only
a
few
regions
of
central
due
limited
availability
genetic
drivers
that
target
specific
throughout
and
adult
life.
This
has
hindered
our
understanding
distinct
interconnect
form
circuits
during
development.
Here,
we
present
split-GAL4
library
composed
driver
lines,
which
generated
via
editing
genomic
locus
lineage-specific
transcription
factors
demonstrate
can
use
this
specifically
most
individual
hemilineages
Drosophila
ventral
nerve
cord
(VNC)
adulthood.
Using
these
found
striking
morphological
processes
within
lineage
metamorphosis.
We
also
demonstrated
neurochemical
features
classes
be
quickly
assessed.
Lastly,
documented
behaviors
elicited
response
optogenetic
activation
comprehensive
lineage-behavior
map
entire
fly
VNC.
Looking
forward,
will
provide
tools
needed
address
questions
emerging
from
analysis
recent
VNC
connectome
transcriptome
datasets.
Sensorimotor
reflex
circuits
engage
distinct
neuronal
subtypes,
defined
by
precise
connectivity,
to
transform
sensation
into
compensatory
behavior.
Whether
and
how
motor
neuron
populations
specify
the
subtype
fate
and/or
sensory
connectivity
of
their
pre-motor
partners
remains
controversial.
Here,
we
discovered
that
neurons
are
dispensable
for
proper
in
vestibular
circuit
stabilizes
gaze.
We
first
measured
activity
following
premotor
projection
after
constitutive
loss
extraocular
partners.
observed
normal
responses
topography
indicative
unchanged
functional
between
neurons.
Next,
show
remain
anatomically
molecularly
poised
connect
appropriately
with
downstream
Lastly,
transcriptional
signatures
typify
develop
independently
Our
findings
comprehensively
overturn
a
long-standing
model:
gaze
stabilization
is
retrogradely
determined
partner-derived
signals.
By
defining
contribution
specification
an
archetypal
sensorimotor
circuit,
our
work
speaks
comparable
processes
spinal
cord
advances
understanding
general
principles
neural
development.
Sensorimotor
reflex
circuits
engage
distinct
neuronal
subtypes,
defined
by
precise
connectivity,
to
transform
sensation
into
compensatory
behavior.
Whether
and
how
motor
neuron
populations
specify
the
subtype
fate
and/or
sensory
connectivity
of
their
pre-motor
partners
remains
controversial.
Here,
we
discovered
that
neurons
are
dispensable
for
proper
in
vestibular
circuit
stabilizes
gaze.
We
first
measured
activity
following
projection
after
constitutive
loss
extraocular
partners.
observed
normal
responses
topography
indicative
unchanged
functional
between
neurons.
Next,
show
remain
anatomically
molecularly
poised
connect
appropriately
with
downstream
Lastly,
transcriptional
signatures
typify
develop
independently
Our
findings
comprehensively
overturn
a
long-standing
model:
gaze
stabilization
is
retrogradely
determined
partner-derived
signals.
By
defining
contribution
specification
an
archetypal
sensorimotor
circuit,
our
work
speaks
comparable
processes
spinal
cord
advances
understanding
principles
neural
development.