European Journal of Cell Biology,
Год журнала:
2024,
Номер
103(4), С. 151466 - 151466
Опубликована: Ноя. 10, 2024
Mammalian
brains
have
evolved
a
neocortex,
which
has
diverged
in
size
and
morphology
different
species
over
the
course
of
evolution.
In
some
mammals,
substantial
increase
number
neurons
glial
cells
resulted
expansion
folding
cerebrum,
it
is
believed
that
these
evolutionary
changes
contributed
to
acquisition
higher
cognitive
abilities
mammals.
However,
their
underlying
molecular
cellular
mechanisms
remain
insufficiently
elucidated.
A
major
difficulty
addressing
stemmed
from
lack
appropriate
animal
models,
as
conventional
experimental
animals
such
mice
rats
small
without
structurally
obvious
folds.
Therefore,
researchers
including
us
focused
on
using
ferrets
instead
rats.
Ferrets
are
domesticated
carnivorous
mammals
with
gyrencephalic
and,
notably,
they
amenable
genetic
manipulations
utero
electroporation
knock
out
genes
cerebrum.
this
review,
we
highlight
recent
research
into
development
evolution
cortical
folds
ferrets.
Folding
of
the
cerebral
cortex
is
a
key
aspect
mammalian
brain
development
and
evolution,
defects
are
linked
to
severe
neurological
disorders.
Primary
folding
occurs
in
highly
stereotyped
patterns
that
predefined
cortical
germinal
zones
by
transcriptomic
protomap.
The
gene
regulatory
landscape
governing
emergence
this
protomap
remains
unknown.
We
characterized
spatiotemporal
dynamics
expression
active
epigenetic
(H3K27ac)
across
prospective
folds
fissures
ferret.
Our
results
show
begins
emerge
at
early
embryonic
stages,
it
involves
cell-fate
signaling
pathways.
H3K27ac
reveals
developmental
restriction
engages
known
regulators,
including
transcription
factor
Cux2
.
Manipulating
progenitors
changed
their
proliferation
pattern
ferret,
caused
selective
transcriptional
changes
as
revealed
single-cell
RNA
sequencing
analyses.
findings
highlight
relevance
mechanisms
defining
folding.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 9, 2025
Abstract
The
strong
size
increase
of
the
human
neocortex
is
supported
both
by
amplification
and
basal
translocation
a
neural
stem
cell
population,
radial
glial
cells
(or
bRG
cells).
Using
live
imaging
second
trimester
fetal
tissue
cortical
organoids,
we
identify
two
independent
modes
for
colonization
neocortex.
On
top
an
actomyosin-dependent
movement
called
mitotic
somal
(MST),
microtubule-dependent
motion
occurring
during
interphase,
that
call
interphasic
(IST).
We
show
IST
driven
LINC
complex,
through
nuclear
envelope
recruitment
dynein
motor
its
activator
LIS1.
Consequently,
severely
altered
in
LIS1
patient-derived
organoids.
also
demonstrate
MST
occurs
prometaphase
spindle
event.
controlled
rounding
molecular
pathway,
via
Moesin
Vimentin,
driving
translocation.
report
85%
due
to
IST,
total
0,67
mm
per
month
gestation.
Our
work
identifies
how
colonize
cortex,
further
shows
are
conserved
bRG-related
migrating
glioblastoma
cells.
Current Opinion in Neurobiology,
Год журнала:
2025,
Номер
93, С. 103046 - 103046
Опубликована: Май 17, 2025
The
cerebral
cortex
is
arguably
the
most
complex
organ
in
humans.
cortical
architecture
characterized
by
a
remarkable
diversity
of
neuronal
and
glial
cell
types
that
make
up
its
circuits.
Following
precise
temporally
ordered
program,
radial
glia
progenitor
(RGP)
cells
generate
all
excitatory
projection
neurons
cell-types.
Cortical
are
produced
either
directly
or
via
intermediate
progenitors,
through
indirect
neurogenesis.
How
extensive
cell-type
generated
during
development
remains,
however,
fundamental
open
question.
do
RGPs
quantitatively
qualitatively
neocortical
neurons?
does
direct
neurogenesis
contribute
to
establishment
lineage
heterogeneity?
Whether
represent
homogeneous
and/or
multipotent
population,
if
consist
heterogeneous
groups
currently
also
not
known.
In
this
review,
we
will
summarize
latest
findings
contributed
deeper
insight
into
above
key
questions.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Июль 30, 2024
Mammalian
brains
vary
in
size,
structure,
and
function,
but
the
extent
to
which
evolutionarily
novel
cell
types
contribute
this
variation
remains
unresolved.
Recent
studies
suggest
there
is
a
primate-specific
population
of
striatal
inhibitory
interneurons,
TAC3
interneurons5.
However,
has
not
yet
been
detailed
analysis
spatial
phylogenetic
distribution
population.
Here,
we
profile
single
gene
expression
developing
pig
(an
ungulate)
ferret
(a
carnivore),
representing
94
million
years
divergence
from
primates,
assign
newborn
neurons
initial
classes
first
specified
during
development.
We
find
that
class
interneurons
represents
an
ancestral
also
deployed
towards
cortex
ferret.
In
adult
mouse,
uncover
rare
expressing
Tac2,
ortholog
TAC3,
ventromedial
striatum,
prompting
reexamination
mouse
interneuron
by
targeted
enrichment
their
precursors.
conclude
conserved
across
Boreoeutherian
mammals,
with
Th
subset
expresses
Tac2.
This
study
suggests
telencephalic
are
largely
evolution,
neuronal
mammalian
brain
change
through
redistribution
fate
refinement,
rather
than
derivation
precursors
early
Abstract
Entosis,
a
form
of
cell
cannibalism,
is
newly
discovered
pathogenic
mechanism
leading
to
the
development
small
brains,
termed
microcephaly,
in
which
P53
activation
was
found
play
major
role.
Microcephaly
with
entosis,
Pals1
mutant
mice,
displays
that
promotes
entosis
and
apoptotic
death.
This
previously
unappreciated
represents
novel
cellular
dynamic
dividing
cortical
progenitors
responsible
for
loss.
To
date,
various
recent
models
microcephaly
have
bolstered
importance
death
microcephaly.
caused
by
mitotic
delay
or
DNA
damage
manifests
can
be
suppressed
removal
these
animal
models.
Such
genetic
studies
attest
as
quality
control
meant
eliminate
genomically
unfit
cells
minimal
involvement
actual
function
associated
genes.
In
this
review,
we
summarize
known
role
variety
introduce
wherein
entotic
cannibalism
neural
triggered
activation.
Brain
development
is
highly
complex
and
dynamic.
During
this
process,
the
different
brain
structures
acquire
new
components,
such
as
cerebral
cortex,
which
builds
up
germinal
cortical
layers
during
its
development.
The
genetic
study
of
structure
has
been
commonly
approached
by
bulk-sequencing
entire
cortex
a
whole.
Here,
we
describe
methodology
to
layered
tissue
in
all
complexity
microdissecting
two
at
developmental
time
points.
This
protocol
combined
with
step-by-step
explanation
dissociation
that
provides
high-quality
cells
ready
be
analyzed
newly
developed
single-cell
assays,
scRNA-seq,
scATAC-seq,
TrackerSeq.
Altogether,
approach
increases
resolution
analyses
from
compared
bulk
studies.
It
also
facilitates
laboratory
animal
models
recapitulate
human
better
than
mice,
like
ferrets.
Key
features
•
Microdissection
individual
developing
living
slices.
Enzymatic
mechanical
generates
suspensions
available
for
high-throughput
assays.
Protocol
optimized
embryonic
early
postnatal
ferret
cortex.