Targets of the transcription factor Six1 identify previously unreported candidate deafness genes
Development,
Год журнала:
2025,
Номер
152(7)
Опубликована: Апрель 1, 2025
ABSTRACT
Branchio-otic
(BOS)
and
branchio-oto-renal
(BOR)
syndromes
are
autosomal
dominant
disorders
featuring
multiple
birth
defects
including
ear,
renal
branchial
malformations.
Mutations
in
the
homeodomain
transcription
factor
SIX1
its
co-factor
EYA1
have
been
identified
about
50%
of
individuals
with
BOS
or
BOR,
while
causative
mutations
unknown
other
half.
We
hypothesise
that
target
genes
represent
new
BOR
candidates.
Using
published
transcriptomic
epigenomic
data
from
chick
ear
progenitors,
we
first
identify
putative
Six1
targets.
Next,
provide
evidence
directly
regulates
some
these
candidates:
binds
to
their
enhancers,
functional
experiments
Xenopus
confirm
controls
expression.
Finally,
show
most
targets
also
expressed
human
developing
associated
known
deafness
loci.
Together,
our
results
not
only
characterise
molecular
mechanisms
mediate
function
but
candidates
for
congenital
deafness.
Язык: Английский
foxg1ais required for hair cell development and regeneration in the zebrafish lateral line
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Апрель 16, 2024
Abstract
Mechanosensory
hair
cells
located
in
the
inner
ear
mediate
sensations
of
hearing
and
balance.
If
damaged,
mammalian
are
unable
to
regenerate,
resulting
permanent
sensory
deficits.
Aquatic
vertebrates
like
zebrafish
(Danio
rerio)
have
a
specialized
class
mechanosensory
found
lateral
line
system,
allowing
them
sense
changes
water
current.
Unlike
cells,
can
robustly
regenerate
following
damage.
In
models,
transcription
factor
Foxg1
functions
promote
normal
development
ear.
Foxg1a
is
expressed
organs
larvae,
but
its
function
during
regeneration
has
not
been
investigated.
We
find
that
loss
results
reduced
cell
regeneration,
as
well
decreased
cellular
proliferation
system.
These
data
suggest
may
be
valuable
target
for
investigation
clinical
regeneration.
Summary
statement
Our
work
demonstrates
role
developing
regenerating
new
through
proliferation.
Язык: Английский
EpCAM regulates hair cell development and regeneration in the zebrafish lateral line.
PubMed,
Год журнала:
2024,
Номер
2024
Опубликована: Янв. 1, 2024
The
zebrafish
lateral
line
mechanosensory
system
shares
considerable
morphological
and
molecular
similarities
with
the
inner
ear.
In
particular,
hair
cells
are
responsible
for
transducing
sensory
stimuli
in
both
structures.
epithelia
cell
adhesion
molecule
(EpCAM)
is
expressed
of
ear
mammals
lines
fish.
EpCAM
regulates
many
cellular
functions
including
adhesion,
migration,
proliferation,
differentiation.
this
study,
we
use
Язык: Английский
foxg1a is required for hair cell development and regeneration in the zebrafish lateral line
Biology Open,
Год журнала:
2024,
Номер
13(9)
Опубликована: Сен. 15, 2024
ABSTRACT
Mechanosensory
hair
cells
located
in
the
inner
ear
mediate
sensations
of
hearing
and
balance.
If
damaged,
mammalian
are
unable
to
regenerate,
resulting
permanent
sensory
deficits.
Aquatic
vertebrates
like
zebrafish
(Danio
rerio)
have
a
specialized
class
mechanosensory
found
lateral
line
system,
allowing
them
sense
changes
water
current.
Unlike
cells,
can
robustly
regenerate
following
damage.
In
mammals,
transcription
factor
Foxg1
functions
promote
normal
development
ear.
Foxg1a
is
expressed
organs
larvae,
but
its
function
during
regeneration
has
not
been
investigated.
Our
study
demonstrates
that
mutation
foxg1a
results
slower
posterior
primordium
migration
delayed
neuromast
formation.
developing
regenerating
neuromasts,
we
find
loss
reduced
cell
numbers,
as
well
decreased
proliferation
cells.
specifically
regulates
Islet1-labeled
These
data
suggest
may
be
valuable
target
for
investigation
clinical
regeneration.
Язык: Английский